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Early life gut microbiota profiles linked to synbiotic formula effects: a randomized clinical trial in European infants.
Lagkouvardos, I, Intze, E, Schaubeck, M, Rooney, JP, Hecht, C, Piloquet, H, Clavel, T
The American journal of clinical nutrition. 2023;117(2):326-339
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Plain language summary
Microbial colonisation of the intestine after birth is a central event that influences infant health with life-long consequences. Although improvement of hygienic conditions reduces infant mortality due to infections, environments with low microbial biomass counteract natural colonisation by commensal microbes. The aim of this study was to assess the effects of a synbiotic intervention formula (IF) on faecal microbiota. This study was a multicentre, randomised, controlled, double-blind intervention trial which enrolled 540 infants. Infants whose parents had chosen not to breastfeed or were not able to breastfeed prior to study inclusion were allocated randomly to 1 of 2 formula groups (n = 230 control formula, n = 230 IF). The infants in the breastfed reference group (n = 80) were mainly fed human milk. Results showed that synbiotic intervention influenced the gut microbiota and milieu parameters during early life to resemble some major characteristics found in breastfed infants (higher relative abundances of bifidobacteria, lower richness, lower faecal pH and butyrate concentrations), and effects depended on the ecosystem profile of the infants. Authors conclude that specific randomised, controlled studies that focus on infants born by Caesarean section and how early nutrition can support the beneficial development of their microbiota are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Infant gut colonisation differs in vaginal versus cesarean section deliveries and between breastfed and infant formula practices.
- Both enriched strain-specific probiotic and standard infant formula were shown to have a marked effect on microbiota colonisation in infants at age 4 months.
- By the age of 2 years, however, there is no significant difference between breastfed and formula fed infants.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This randomised controlled intervention study compared gut health parameters with the use of a synbiotic pre- and probiotic strain enriched infant formula with human milk and standard formula at three intervals over a period of 2 years.
Methods
This was a double-blinded controlled study of 540 infants from France and Belgium. Participants were randomly allocated to 2 formula groups (n = 230 Control Formula (CF), n = 230 Intervention Formula (IF)) and the breastfed reference group (n = 80) as well as delivery mode (Cesarean and vaginal delivery). The synbiotic IF was a standard infant formula enriched with prebiotic GOS (0.02 g/g) and the probiotic strain L. fermentum CECT5716 (at least 1.0 × 106 cfu/g).
Stool analysis was conducted at three time intervals, 4, 12, and 24 months (infant age). Biomarkers included short chain fatty acids, pH, secretory IgA, calprotectin, and various bacterial phyla via microbiota analysis.
Results
- At 4 months, the IF group tested higher for Bifidobacterium spp., and Lactobacillaceae and lower occurrence of Blautia spp., as well as Ruminoccocus gnavus and relatives compared to CF. They also had lower fecal pH and butyrate levels
- Both the formula cohorts had lower SigA and more basic pH values than the human milk cohort, as well as higher prevalence of anaerobes belonging to the bacterial genera Akkermansia, Collinsella, and Faecalibacterium.
- By age 24 months, the IF cohort exhibited increased levels of Akkermansia, Escherichia-Shigella, and R.gnavus. However there were no significant differences between the formula fed and human milk cohort at this time interval.
- The differences observed at 4 months disappeared over time, except for a significantly higher relative abundance of bifidobacteria and Faecalibacterium spp. in IF infants at 12 months compared with CF infants.
Conclusion:
Although prominent differences between the cohorts were observed at 4 months, it appears that by the age of 2 years, there is little observable difference. This is most likely due to gut ecosystem maturation. The paper draws attention to the fact that changes to microbiota following treatment were more pronounced in infants who tested lower in occurrences of Bacteroides spp at age 4 months. Of note is the prevalence of cesarean birth deliveries in this cohort thereby indicating potential improved alternative feeding options when breastfeeding is not possible for these infants.
Clinical practice applications:
- Probiotic L.fermentum and prebiotic galacto-oligosaccharide enriched infant formula appears to the improve infant microbiome, when compared to that of breastfed infants.
- The most receptive infants were those born via cesarean section.
Limitations to consider:
- The sample groups were from France and Belgium, with no indication as to culture, socio-economic, or sex distribution.
- The two infant formula groups were n=230 each with only 80 infants in the breastfed reference group.
- There was no indication of maternal diet practices pre-, during, and post- pregnancy.
- Stool samples were not collected from the infants at baseline visit prior to formula intervention.
Considerations for future research:
- Future studies need to include more diverse cultural and socio-economic cohorts to ascertain the potential influence of parental diet in baseline infant microbiome.
- It is imperative to establish what role solid food choices, generally introduced at 6 months, might have on gut ecosystem maturation.
- It would be useful to have a larger cesarean section birth cohort to compare to vaginal deliveries for more definitive results.
Abstract
BACKGROUND Microbial colonization of the gastrointestinal tract after birth is an essential event that influences infant health with life-long consequences. Therefore, it is important to investigate strategies to positively modulate colonization in early life. OBJECTIVES This randomized, controlled intervention study included 540 infants to investigate the effects of a synbiotic intervention formula (IF) containing Limosilactobacillus fermentum CECT5716 and galacto-oligosaccharides on the fecal microbiome. METHODS The fecal microbiota from infants was analyzed by 16S rRNA amplicon sequencing at 4, 12, and 24 months of age. Metabolites (e.g., short-chain fatty acids) and other milieu parameters (e.g., pH, humidity, and IgA) were also measured in stool samples. RESULTS Microbiota profiles changed with age, with major differences in diversity and composition. Significant effects of the synbiotic IF compared with control formula (CF) were visible at month 4, including higher occurrence of Bifidobacterium spp. and Lactobacillaceae and lower occurrence of Blautia spp., as well as Ruminoccocus gnavus and relatives. This was accompanied by lower fecal pH and concentrations of butyrate. After de novo clustering at 4 months of age, overall phylogenetic profiles of the infants receiving IF were closer to reference profiles of those fed with human milk than infants fed CF. The changes owing to IF were associated with fecal microbiota states characterized by lower occurrence of Bacteroides compared with higher levels of Firmicutes (valid name Bacillota), Proteobacteria (valid name Pseudomonadota), and Bifidobacterium at 4 months of age. These microbiota states were linked to higher prevalence of infants born by Cesarean section. CONCLUSIONS The synbiotic intervention influenced fecal microbiota and milieu parameters at an early age depending on the overall microbiota profiles of the infants, sharing a few similarities with breastfed infants. This trial was registered at clinicaltrials.gov as NCT02221687.
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Efficacy of diet restriction with or without probiotic for treatment of patients with IBS-D: Phase I-II clinical trial.
Zhao, XS, Shi, LJ, Ning, BL, Zhao, ZM, Li, XX, Zhu, MH, Zhang, YB, Fu, J
Immunity, inflammation and disease. 2023;11(5):e857
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Irritable bowel syndrome (IBS) is a functional intestinal disorder that can significantly affect quality of life. IBS patients suffer from intermittent abdominal pain/ discomfort, altered bowel habits, and abdominal bloating/distension. The aim of this study was to assess the effects of dietary restriction and probiotic use on IBS‐D patients. This study was a 2 × 2 factorial design, single‐centre, randomised trial. Phase 1 was a 12‐week dietary intervention, with 214 participants randomised to an IgG positive restricted diet (IgG res diet) or a control diet (cold/spicy/fried restricted). In Phase 2, 167 participants were randomised into either an IgG res diet + placebo or an IgG res diet + probiotic for 12 weeks. Symptom Severity Scale (IBS‐D‐SSS) and IgG titer were assessed at the beginning and the end of the study. Results showed that both diets reduced IBS‐D symptom severity scores and decreased immunoglobulin (IgG) antibody titer, although the IgG res diet had a greater impact. IBS symptom scores decreased with the addition of a Bifidobacterium probiotic along with dietary exclusion, however, IgG titers did not change with the probiotic compared to placebo. Authors concluded that diet restriction with appropriate and effective probiotics, provides greater symptom reductions for patients with IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
For individuals with IBDS-D:
- Establish IgG intolerances to foods and ensure an elimination diet remains nutritionally balanced
- Consider combining elimination diet with a Bifidobacterium supplement.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Irritable bowel syndrome (IBS) is a common functional intestinal disorder, affecting 5-20% of the population and diet is likely a major factor in its development as well as in its management. The aim of this study was to compare 3 dietary interventions and the use of a probiotic supplement in patients with IBS-diarrhoea dominant (IBS-D).
Methods
The study was conducted in 2 phases. The first was a 12-week 2 × 2 factorial design, randomised dietary intervention and included 224 patients (214 completed) with IBS-D. The diets were an Eastern/Chinese restriction diet, avoiding cold/raw, spicy and fried foods (CSF), the second avoided common allergens as determined by an IgG test (IgG diet, 14 foods tested), the third a combination of the two, whilst the control group continued their usual (Eastern/Chinese) diet.
The second phase was a 12-week randomised, double-blind, placebo-controlled trial comparing the CSF + IgG diet plus placebo with the CSF + IgG diet plus a 2 billion Bifidobacterium adolescentis supplement; this part included 202 patients of whom 169 completed the study.
The primary outcomes under observation were a reduction in IBS-D symptom severity Score (IBS-D-SSS) and IgG antibody titre (TigG).
Results
Phase 1: The IBS-D-SSS improved in all four groups from baseline (p<0.001), with the intervention groups improving significantly more than the control group (p<0.001). There was no statistically significant difference between the IgG and the IgG + CSF groups, although the authors considered there to be a synergistic effect. Statistically significant (p<0.001) reductions in TIgG were seen in all interventions, but not the control group.
Part 2: Significant (p<0.001) improvements in IBS-D-SSS were seen with both placebo and Bifidobacterium, although this was greater in the probiotic group (p<0.001). Improvements in TIgG were seen in both groups (p<0.001), with no difference between groups.
Conclusion
The authors concluded that the best intervention for patients with IBD-D is an IgG food elimination diet together with a Bifidobacterium probiotic supplement.
Clinical practice applications:
- Consider an elimination diet based on IgG testing for clients with IBS-D
- Consider combining elimination diet with a Bifidobacterium supplement. The dose used in this study was 4x 0.5 billion capsules of Bifidobacterium adolescentis
- Eliminating cold/raw, spicy and fried food could be an alternative to IgG elimination if the latter is not suitable for the client.
Considerations for future research:
- 45% and 35% of screened patients, respectively in the 2 phases of the study, were IgG negative. Screening for more potential food intolerances may extend the suitability of the approach to more patients
- Only a single strain probiotic was tested. Further research could evaluate other or combinations of Bifidobacteria strains in combination with an IgG elimination diet
- The mechanism(s) by which probiotics may affect symptoms of IBS-D are unknown. Adding stool microbiome analyses may shed further light on the effect of the intervention on the composition and function of the microbiome.
Abstract
BACKGROUND AND AIM Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. METHODS Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. RESULTS Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. CONCLUSIONS Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.
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Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.
Ma, T, Yang, N, Xie, Y, Li, Y, Xiao, Q, Li, Q, Jin, H, Zheng, L, Sun, Z, Zuo, K, et al
Pharmacological research. 2023;191:106755
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Chronic constipation (CC) is a common gastroenterological problem encountered in clinical practice, and it negatively impacts patients’ quality of life. Growing evidence indicates that the occurrence of CC is closely linked to gut dysbiosis. Several main probiotics have been used to relieve constipation. The main aim of this study was to systematically evaluate the beneficial effects of Lactiplantibacillus plantarum P9 (P9) administration on alleviating CC and impact on the host gut microbiota and its metabolites. This study was a 42-day longitudinal double-blind randomised controlled trial which enrolled a total of 181 patients with CC. Subjects were randomly assigned to the probiotic or placebo group. Subjects in P9 group received one sachet of P9 powder per day after meal. Results show that P9 administration significantly improved patients’ defecation frequency. In fact, P9 administration effectively alleviated constipation, and the symptom relief effects were linked to desired changes and interactions with different types of host microbes. Authors conclude that administering P9 could effectively relieve chronic constipation in adults and improve some aspects of their quality of life.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study suggested that P9-associated constipation symptom relief was not attributed to macroscopic changes in the host gut bacteriome and phageome
- However, results supported that taking P9 could alleviate constipation, with the symptom relief effects linked to desired changes and interactions with different types of host microbes, including the gut commensal bacteria (L. plantarum, Ruminococcus_B gnavus, Oscillospiraceae sp., Lachnospiraceae sp.) and the bacteriophage family, Herelleviridae.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study investigated the effect of a specific probiotic strain in alleviating Chronic Constipation (CC).
Methods
- The study employed a 42-day randomised control trial (RTC) double-blind, placebo-controlled design, with 163 patients, (mean age =22.68 ±5.66 years for the probiotic group and 21.59 ±4.59 years for the placebo group), diagnosed with CC (Rome IV criteria)
- The male to female ratio was 15–63 and 17–68 in probiotic and placebo groups respectively
- Groups were standardised with no differences observed in baseline age, gender ratio, drug treatment, high-fibre diet and smoking between the two groups (P >0.18)
- Participants were randomly assigned to the probiotic Lactiplantibacillis plantarum P9 (n=78; 2 g per sachet, 1 ×1011 CFU/day) or the placebo (n =85; maltodextrin powder) groups.
Results
Primary outcomes: weekly mean complete spontaneous bowel movements (CSBMs):
- At 28-days CSBM was 28% higher in the P9 group (P=0.039) compared with the placebo group
- At 42-days CSBM remained significantly higher in the P9 group (P=0.026) compared with the placebo group, and increased 2-fold compared with baseline (P <0.05)
- Authors noted that the CSBM benefits were maintained even after 14 days of not taking the supplement.
Secondary outcomes: The effects of P9 supplementation on constipation-related parameters, including the weekly mean frequency of spontaneous bowel movements (SBMs) demonstrated:
- After 28-days of P9 supplementation, SBMs were 12% higher than the placebo group (P=0.039)
- No differences were observed in the weekly mean stool consistency and straining scores between groups (P>0.05).
Patients’ quality of life and psychological state, using a PAC-QOL questionnaire related to: worries and concerns (WO), physical discomfort, psychosocial discomfort, and satisfaction and found:
- At day 14 WO in the P9 group was 1.22-fold lower than those in the placebo group (P <0.05)
- No differences in the other 3 items between P9 and placebo groups (P >0.05) were observed
- Supplementation resulted in a significant change in relative abundance of the P9 genome (≥0.01%)
- However, no differences were observed in alpha diversity after P9 consumption compared with placebo.
Conclusion
- The results indicated that P9 administration alleviated patients’ constipation symptoms and improved their quality of life but did not impact on gut bacteria or phageome
- Lactiplantibacillis plantarum P9 supplementation impacted several beneficial bacteria species (e.g. (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), and reduced levels of other bacteria and phage taxa (e.g. Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae) which may be implicated in constipation relief mechanisms.
Clinical practice applications:
- In this study, the use of P9 administration significantly improved patients’ defecation frequency which could have beneficial implications for patients suffering from chronic constipation
- Probiotic effects are known to be strain- and host-specific, and based on this study P9 administration for relief of constipation needs to be taken for at least two weeks to improve aspects of patients’ quality of life and 4 weeks for improvements in constipation.
Considerations for future research:
- Future trials should include factors that impact gut motility and constipation symptoms, such as: a detailed daily diet (dietary composition, fibre content, and water intake) and physical activity scale (intensity and duration), and longer term use of P9 or comparison across strains
- The relatively small study size and short duration of this study, as well as the younger age groups included may be pertinent when considering future research.
Abstract
Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.
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Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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5.
Bifidobacterium longum subsp. longum Reduces Perceived Psychological Stress in Healthy Adults: An Exploratory Clinical Trial.
Boehme, M, Rémond-Derbez, N, Lerond, C, Lavalle, L, Keddani, S, Steinmann, M, Rytz, A, Dalile, B, Verbeke, K, Van Oudenhove, L, et al
Nutrients. 2023;15(14)
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Psychosocial stress is a common issue and one way in which nutrition may modulate the stress response is via the microbiota-gut-brain axis. This 6-week randomised, double-blind, placebo-controlled trial of 45 healthy adults with mild-to-moderate stress evaluated the effects of Bifidobacterium longum (BL) NCC3001 on psychological and physiological markers of stress and the response to an acute stress test. Outcome measures included cortisol awakening response, heart rate, heart rate variability and various questionnaires assessing stress, anxiety, depression, sleep and gastrointestinal symptoms. Compared to placebo, probiotic intake led to a significant decrease in perceived stress and an improvement in subjective sleep after 6 weeks. There was no difference in cortisol awakening response. The subjects in both groups did not experience significant gastrointestinal symptoms and scored low on anxiety and depression at baseline. In response to the acute stress test, cortisol levels were higher in the probiotic than the placebo group, whilst no clear differences were seen in heart rate and heart rate variability. Subjects in the probiotic group had a lower pain experience during the stress test whilst subjects in the placebo group had an increase in positive mood following the test. The authors conclude that these results support their hypothesis that BL NCC3001 may alleviate stress and improve sleep in adults with moderate stress levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There is mounting evidence to suggest that nutritional interventions can influence our stress responses. One of the routes by which nutrition can influence physiological and psychological stress responses involves the microbiota– gut–brain-axis.
- This exploratory trial suggests that supplementation with Bifidobacterium longum (BL) strain NCC3001 leads to a beneficial effect on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomised, placebo-controlled, two-arm, parallel, double-blind exploratory clinical trial was conducted to investigate the effect Bifidobacterium longum (BL) strain NCC3001 on stress-related psychological and physiological parameters and acute stress in healthy adults who typically experience mild-to-moderate-levels of stress.
Method
47 Participants between the ages of 25-65 years old with mild-to-moderate psychological stress received 1x1010 CFU of Bifidobacterium longum (BL) strain NCC3001 daily or a placebo for 6 weeks.
Participants completed the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scales (HAD-A and HADS-D), the Gastrointestinal Symptom Rating Scale (GSRA), the Pittsburgh Sleep Quality Index (PSQI) questionnaire, the Positive and Negative Affect Schedule (PANAS), the State Trait Anxiety Inventory (STAI-6), the Maastricht Acute Stress Test (MAST) and the Visual Analog Scales (VAS, which measures pain intensity) during the clinical study. The Depression, Anxiety and Stress Scale (DASS-42) questionnaire was also used to depict the progression of the participants through the study.
Faecal samples were taken at baseline and 6 weeks and awakening saliva samples were taken at baseline, 2, 4, 6 and 8 weeks. At the endpoint, 45/49 (91%) of the subjects completed the study. One participant reported an adverse event and the other withdrew without an explanation. Two participants were excluded from the full analysis.
Results
The primary outcomes were:
- After 6-week of the probiotic intervention, there was a significant decrease in perceived stress in the probiotic group (21.4%) compared to the placebo group (-10.2%), p = 0.017.
- There was a significant improvement in subjective sleep in the probiotic group compared to the placebo group (p = 0.037).
- There was a significant decrease in the positive PANAS change score from the pre-stressor stage in the probiotic group compared to the placebo group (p = 0.01).
- There were lower pain values (VAS) scores from pre-stressor to post-stressor in the probiotic group compared to the placebo group (p = 0.05).
- There was no significant difference between groups in anxiety (HADS-A) and Depression (HADS_D) scores.
Conclusion
Oral supplementation with BL NCC3001 may have beneficial effects on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
Clinical practice applications:
- While the mechanism underlying the correlation between the microbiota and the gut-brain-axis is not fully understood, it is thought to play a critical role in the links between the microbiota, mood, stress, and brain health.
- This exploratory trial additionally supports the potential of specific probiotics being used to reduce perceived stress and improve subjective sleep quality in healthy adults.
Considerations for future research:
- Larger, powered clinical trials are needed to provide further insights into the mechanisms underlying the stress-relieving and sleep-improving effect of Bifidobacterium longum.
- Furthermore, the dosage and duration of the probiotics need further investigation in a larger healthy population.
- Comparative research is needed to help investigate the effect of different probiotic strains on stress relief and sleep quality.
Abstract
Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.
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6.
Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome.
Martoni, CJ, Srivastava, S, Damholt, A, Leyer, GJ
World journal of gastroenterology. 2023;29(28):4451-4465
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Plain language summary
Probiotics are microorganisms that have been shown in previous research to improve symptoms of diarrhoea-predominant irritable bowel syndrome (IBS-D). This randomised control trial of 307 individuals with IBS-D aimed to determine the tolerability and efficacy of varying doses of the microbiota Lactiplantibacillus plantarum. The results showed that the severity of symptoms improved with L. plantarum regardless of whether individuals were given a high or low dose. Improvements were seen as soon as 28 days following supplementation. Abdominal pain severity, duration, bloating, bowel movements, and quality of life were all improved. Individuals in the study largely tolerated the supplement, with only a few occurrences of nausea and vomiting. It was concluded that L. plantarum is effective and safe for improving symptoms associated with IBS-D. This study could be used by healthcare professionals to recommend L. plantarum supplementation to individuals with hard to treat or persistent IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This randomised, double-blind, placebo controlled, multi-centre, parallel-arm and dose-ranging study showed that L. plantarum may be a strong candidate for the management of IBS-D symptoms and associated mental health effects.
- L. plantarum may be of particular benefit to individuals who are suffering from stress because of IBS-D.
- L. plantarum is well tolerated and may be of benefit to individuals who have ceased pharmaceutical treatments as a result of side-effects.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the tolerability and efficacy of varying supplemental doses of Lactiplantibacillus plantarum (Lpla33) in adults with irritable bowel syndrome of the diarrhoea predominant subtype (IBS-D).
Methods
This randomised, double blind, placebo-controlled trial recruited 307 females and males aged 18-70 years with IBS-D based upon the Rome IV diagnostic criteria with Bristol Stool Scale stools of type 6 or 7.
Individuals were randomised to receive an eight-week intervention in one of three study groups: Group 1B: Lpla33 at 1 × 109 vs group 10B: 1x1010 colony forming units (CFU) per day vs placebo.
Results
- Improvement was seen in the primary outcome of IBS-D symptom severity (IBS-SSS) with both Lpla33 doses compared to placebo at the end of the trial (P=<0.001).
- Improvements with both doses compared to placebo were seen as quickly as 28 days (P=<0.01).
- At the end of the study the higher dose Lpla33 was more effective at improving IBS-SSS compared to the lower dose (P=<0.05).
- Improvements to IBS remission or mild IBS were seen in 48.1% in group 1B, 72.6% in group 10B and only 11.1% of placebo (P=<0.001).
- Specific improvements were seen in 10B group compared to placebo in abdominal pain severity and duration, abdominal distension, bowel habits, and quality of life (QoL) (P=<0.001).
- Post-hoc analysis showed that supplementation prevented symptom development compared to placebo with 2.9% of group 1B, 2.1% of group 10B and 18.2% of placebo individuals reporting increased symptom severity (P=<0.001).
- QoL and perceived stress were improved with supplementation compared to placebo (P=<0.001 for both), with the higher dose being more beneficial than the lower dose in QoL (P=<0.001).
- Compliance to Lpla33 was comparable to placebo (P=>0.05), with adverse events related to the supplement including nausea and vomiting.
Conclusion
- L. plantarum at doses of 1 × 109 and 1 × 1010 CFU/day is a well-tolerated and efficacious therapy for the improvement of symptoms related to IBS-D, with benefits seen as quickly as 28 days after commencing supplementation.
- Symptoms such as abdominal pain severity and duration, QoL and perceived stress may all be improved.
- Stool normalisation may be seen in certain individuals.
Clinical practice applications:
- L. plantarum supplementation may be of benefit to the management and improvement of symptoms in individuals with IBS-D.
- Improvements may be seen physically and in mental health parameters.
- Metronidazole (400mg/day) was given as a rescue medication for individuals with severe pain and frequent loose stools and should be considered when interpreting results.
Considerations for future research:
- The authors concluded that future research should focus on understanding the mechanisms of action that may be involved.
- Studying the role of diet on the microbial community and metabolite profiles in IBS-D may be of interest.
Abstract
BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates. AIM: To investigate the clinical efficacy of Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428) in adults with IBS-D. METHODS This is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress. RESULTS IBS-SSS was significantly reduced, after 8 wk, in participants receiving L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group (P < 0.001). In contrast, no significant shifts were observed in microbial diversity. CONCLUSION L. plantarum Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.
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7.
Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Oh, JH, Jang, YS, Kang, D, Kim, HS, Kim, EJ, Park, SY, Kim, CH, Min, YW, Chang, DK
Gut and liver. 2023;17(1):100-107
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Plain language summary
Irritable bowel syndrome (IBS) affects 1 in 10 people globally and is a common health problem for the elderly. Recent studies have shown that changes in the gut microbiome may play an important part in IBS and there is evidence that using pre and pro biotics have positive effects on IBS. The aim of this randomized, double-blind, placebo-controlled trial was to determine the effects of a new synbiotic formulation (L. paracasei DKGF1 and prebiotics extracted from O. humifusa) on GI symptoms in elderly patients with IBS. 67 participants were randomly divided into 2 groups. For 4 weeks one group took the synbiotic and the other group took a placebo. Symptoms were recorded via questionnaires. The consumption of the synbiotic combination was associated with overall relief of IBS symptoms in elderly patients. In particular, abdominal pain and psychological well-being noticeably improved. In conclusion this synbiotic is effective and safe to use in elderly patients with global IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The management of IBS in elderly people is more complicated than in younger populations.
- Synbiotic formulations containing both probiotics and prebiotics have reported gastrointestinal health benefits.
- This randomized controlled trial indicated that the synbiotic containing L. paracasei DKGF1 and Optuntia humifusa extracts might be effective and safe for treating IBS symptoms in elderly patients.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This study involved a randomized, double-blind, placebo-controlled trial to investigate the impact of a synbiotic combination, comprising of L. paracasei DKGF1 and prebiotics extracted from Optuntia humifusa, on Irritable Bowel Syndrome (IBS) in elderly patients.
Method
Sixty-seven IBS patients (mean age: 64 years) were randomly assigned to either a synbiotic group (n=33) or a placebo group (n=34) for a 4-week intervention. The synbiotic group received a daily sachet containing one billion colony-forming units of L. paracasei DKGF1, 0.2g of O. humifusa extract and 1.59 grams of maltodextrin, while the placebo group received an identical sachet containing only maltodextrin.
During the study period
- Participants recorded the degree of symptom improvement using a Subject Global Assessment (SGA) scale.
- IBS symptoms, abdominal pain, gas, bloating, and psychological well-being were recorded using a Visual Analogue Scale (VAS).
- Stool form and consistency were assessed using a Bristol Stool Chart (BSC).
Results
The primary findings from the study were as follows:
- There was significant improvement in IBS symptoms as measured by the SGA score, in the synbiotic group versus the placebo group (+50.5% vs +23.5%, p=0.017). The synbiotic group consistently demonstrated improved response rates.
The secondary findings were as follows:
- Participants also reported an improvement in psychological well-being in the synbiotic group (from 1.3 to 1.0) compared to the placebo group (from 3.0 to 2.0) (p=0.003).
- Responders reported a significant improvement in stool form and consistency in the synbiotic group (+85.7%) compared to the placebo group (+22.2%) (p=0.04).
- Among the patients with IBS constipation, patients in the synbiotic group reported a positive response compared to the placebo group (0% and +100%, p=0.029).
- . However, there was no significant improvement among the patients with IBS diarrhoea in the synbiotic group compared to the placebo group (+33.3% and +66.6%,, p=0.52).
Conclusion:
This randomized, double-blind, placebo-controlled trial, reported that the synbiotic combination of L. paracasei DKGF1 and Optuntia humifusa, may be associated with the relief of IBS symptoms in elderly patients, particularly in terms of abdominal pain and psychological well-being.
Clinical practice applications:
- The human microbiota undergoes changes in diversity and variation with age, emphasising the importance of understanding age-specific interventions.
- Managing IBS in the elderly is challenging, and synbiotics, containing both probiotics and prebiotics, have reported gastrointestinal health benefits.
- Most clinical trials have excluded elderly patients, and there has been uncertainty about whether synbiotic use is safe for the elderly.
- This study focused exclusively on elderly patients with IBS, indicating the potential safety and effective use of a synbiotic containing L. paracasei DKGF1 and Optuntia humifusa in improving IBS symptoms.
Considerations for future research:
- Only elderly patients were included in this study, therefore further investigation is needed to explore the effects of synbiotics on participants of different age groups.
- Microbial analysis was not done in this study. It would be useful to include this in future research to gain more insight into the microbiome’s diversity in elderly patients with IBS.
- The study did not quantify food intake or variety which might have impacted the results, therefore future research needs to consider the impact diet has on the microbiome and IBS.
- Since patient reports are subjective, future research should consider involving researchers during patient-reported assessments to enhance the accuracy and reliability of the data.
Abstract
BACKGROUND/AIMS: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. METHODS Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebo group (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. RESULTS Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological well-being (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. CONCLUSIONS The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.
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8.
B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine.
Bager, P, Hvas, CL, Hansen, MM, Ueland, P, Dahlerup, JF
Molecular medicine (Cambridge, Mass.). 2023;29(1):143
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Plain language summary
IBD is characterised by chronic inflammation of the gastrointestinal tract with periodic inactive (quiescent disease) and periodic active inflammation. Chronic fatigue is regarded as elevated fatigue levels with duration of more than 6 months. Malnutrition in patients with IBD is well known and this study assessed changes in B-vitamins and their related metabolites directly after high dose oral thiamine, vitamin B1. 40 adult patients with quiescent IBD and chronic fatigue were randomised compared to a control group of 20 patients without fatigue. In total, 52 females and 8 men took part in the trial. Half of the patients had Crohn’s disease and half had ulcerative colitis. Blood samples were taken and patients answered questionnaires regarding fatigue at each study visit. The researchers found low levels of Flavin mononucleotide (FMN), a biomolecule produced from riboflavin (vitamin B2) in patients with chronic fatigue in comparison to patients without fatigue. The researchers also observed that fatigued IBD patients had a less diverse microbiome with reduced numbers of butyrate-producing bacterial species compared to non-fatigued patients, highlighting the importance of vitamin B1 for the growth of gut bacteria. The oral dose of vitamin B1 administered is unclear and other factors influencing fatigue such as diet, sleep and physical activity were not investigated. The researchers conclude the mechanisms of B-vitamins in IBD in relation to fatigue does require further exploration along with assessing vitamin B2’s effect on IBD fatigue.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This was a small secondary analysis of samples and data from a previous RCT and further investigations would be of benefit to confirm findings.
- However, low plasma B2 vitamin and FMN levels may be associated with chronic fatigue in individuals with IBD.
- Thiamine supplementation may result in higher use of riboflavin and ways to support these should be considered and may improve outcomes in this patient group.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Fatigue is considered a symptom of inflammatory bowel disease (IBD), and may be related to nutrient deficiencies and inflammation. Thiamine is an essential vitamin in the biosynthesis of adenosine triphosphate and energy, however deficiency amongst individuals with IBD is not common and so not monitored. This study aimed to compare plasma B vitamin levels, and their related metabolites and vitamers of individuals with quiescent IBD either with fatigue or without fatigue and determine the effect of high dose thiamine on fatigue.
Methods
- This was a secondary analysis of blood plasma samples collected from a previous randomised control trial (RCT), which looked at the supplementation of high dose thiamine on levels of fatigue in individuals with IBD.
- Samples were available from 60 individuals with IBD; 40 individuals with quiescent IBD and chronic fatigue. 20 individuals with quiescent IBD and no fatigue.
- 21 B vitamins and their associated metabolites and vitamers were analysed.
Results
- Of the 21 measures, only flavin mononucleotide (FMN), a B2 vitamer, was different between those with IBD and fatigue and those with IBD without fatigue. Those with fatigue had lower median FMN levels than those without (11.1 nmol/L; IQR 8.4 to 13.7 vs 14.2 nmol/l; IQR 10.9 to 17.0; P= 0.02).
- Thiamine treatment amongst those with fatigue increased thiamine levels, but had no effect on other metabolites or vitamers (statistics not given).
- Individuals with fatigue who improved with thiamine treatment showed a drop in riboflavin levels after therapy was given (P=0.01), whilst all other B vitamins, vitamers, and metabolites stayed the same.
Conclusion
- It was concluded that amongst the vitamers, metabolites, and B vitamins analysed, only FMN and riboflavin are associated with chronic fatigue in individuals with IBD.
Clinical practice applications:
- Low FMN may be involved in the development of fatigue in individuals with IBD.
- This trial did not show if vitamin B2 supplementation would be of benefit to individuals with IBD and chronic fatigue.
- Lower riboflavin levels following thiamine supplementation may be associated with an increase in its use for thiamine mediated ATP production.
- This study may be able to inform future research or support the supplementation of B2 if further research is found.
- Blood plasma levels of other B vitamins and their metabolites and vitamers is unlikely to be related to chronic fatigue in individuals with IBD.
- Use of the IBD fatigue questionnaire may be of utility in clinical practice.
Considerations for future research:
- Larger RCTs, which have been designed to analyse this specific research question are warranted, as this study was conducted in a small number of individuals as a secondary analysis of samples from another RCT.
- Supplementation RCTs of vitamin B2 alone and in combination with thiamine on individuals with IBD and chronic fatigue would be of benefit.
Abstract
BACKGROUND High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.
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9.
Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.
Shin, JH, Kim, CS, Cha, L, Kim, S, Lee, S, Chae, S, Chun, WY, Shin, DM
The Journal of nutritional biochemistry. 2022;99:108854
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Plain language summary
Disturbances in a person’s mood interrupts their personal well-being and the ability to participate in social interactions, leading to physical health problems such as chronic diseases. The role of diet as a mood regulator has received a great deal of interest. Certain dietary components have been shown to reduce anxiety and depression and improve quality of life. The aim of this study was to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. This study is a randomized controlled trial. Participants who met the criteria for eligibility were randomly assigned to one of three groups: (1) control group (CON, n=14); 2) 85% cocoa chocolate group (DC85, n=18); and 3) 70% cocoa chocolate group (DC70, n=16). Results show that daily intake of dark chocolate significantly reduced negative affect in the DC85, but not in the DC70. Furthermore, gut microbial diversity was significantly higher in DC85 than the CON. Authors conclude that dark chocolate has prebiotic effects by restructuring the diversity and composition of the gut microbiome, which may in turn improve mood via the gut-brain axis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of high cocoa content dark chocolate in relation to mental states
- To promote more awareness of how dietary habits may impact emotional wellbeing
- To emphasise the importance of microbiota and the gut-brain axis regarding dietary habits.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
The authors highlight that dark chocolate has been continually identified for its effects on mood. However, there is a dearth of evidence concerning the emotional impact of daily consumption of dark chocolate. Hence, the impact of dark chocolate consumption on daily mood, focusing on the gut-brain axis, is being investigated in this study.
Objectives
- To evaluate the correlation between the effect on emotional state after consuming dark chocolate and the gut microbiota in healthy adults
- To identify alterations in the composition and diversity of the microorganisms in the gastrointestinal tract on account of dark chocolate intake.
Study Design
A randomised controlled trial was performed at Seoul National University from July to December 2017, This involved. consumption of two types of dark chocolate (70% and 85% cocoa content). Subjects in the treatment groups were blinded although investigators and the control cohort were unblinded.
Participants
117 individuals were screened. However, 48 healthy males and females aged 20-30 years were eligible at baseline.
Interventions
- Subjects (n=16): Consumed 30g/day of 70% cocoa chocolate for 3 weeks
- Participants (n=18): Consumed 30g/day of 85% cocoa chocolate for 3 weeks
- Participants (n=14): The control group consumed no chocolate for 3 weeks.
Main Health Outcomes Measured
- Mood states were quantified via the Positive and Negative Affect Schedule in tandem with Microbiota analysis pre- and post-experiment
- Body composition analysis and dietary assessment were also conducted pre- and post-intervention
- Faecal 16S rRNA sequencing analysis of bacterial genomic DNA was conducted for the cohort who consumed 85% cocoa chocolate and the control arm to evaluate the association between the mood-altering effects of dark chocolate and the gut microbiota
- Statistical tests were performed based on intention-to-treat analysis. The Chi-squared test, Kruskal-Wallis test, one-way ANOVA, unpaired t-test and Mann-Whitney U test were employed for inter-group analysis. Spearman's correlation analysis was used to assess the association between gut microbiota composition and mood scores and P<.05 was considered statistically significant.
Results
- Daily intake of dark chocolate substantially diminished negative emotional states in the cohort consuming 85% cocoa content, but not in the 70% cocoa treatment arm
- Gut microbial diversity was substantially greater in the 85% cacao cohort than the control group (P<.05)
- Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were decreased in the 85% cacao cohort than the control arm (P<.05).
- Furthermore, it was observed that changes in negative affect scores were inversely correlated with diversity and relative abundance of Blautia obeum (P<.05).
Conclusions
The observations suggest that consumption of dark chocolate with a higher cocoa content may induce prebiotic effects due to its capacity to restructure the diversity and composition of the gut microbiota. Furthermore, consuming dark chocolate with a higher cocoa might exert a positive effect on negative emotional states through the gut-brain axis.
Clinical practice applications:
- To inform practitioners of the benefits of 30g/day high (85%) cocoa chocolate consumption and its potential positive impact on mood through the gut-brain axis
- To educate clients regarding the potential benefits of daily high cocoa content chocolate consumption and its possible favourable effect on emotional states associated with gut microbiota.
Considerations for future research:
- More extensive research could investigate interventions of a longer period
- Further studies could evaluate if any difference exists between cocoa and cacao consumption and emotional states via the gut-brain axis, and the strength of any associations
- Interventions could investigate which strains of bacteria that high cocoa content dark chocolate may affect.
Abstract
Dark chocolate has long been recognized for its mood-altering properties; however, the evidence regarding the emotional effects of daily dark chocolate intake is limited. Therefore, we aimed to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. Two different dark chocolates (85% and 70% cocoa content) were tested in this study. In a randomized controlled trial, healthy adults (20-30 y) consumed either 30 g/d of 85% cocoa chocolate (DC85, n=18); 70% cocoa chocolate (DC70, n=16); or no chocolate (control group, CON; n=14); for 3 weeks. Mood states were measured using the Positive and Negative Affect Schedule (PANAS). Daily consumption of dark chocolate significantly reduced negative affect in DC85, but not in DC70. To assess the association between the mood-altering effects of dark chocolate and the gut microbiota, we performed fecal 16S rRNA sequencing analysis for the DC85 and CON groups. Gut microbial diversity was significantly higher in DC85 than CON (P<.05). Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were reduced in DC85 compared to CON (P<.05). Furthermore, we found that the observed changes in negative affect scores were negatively correlated with diversity and relative abundance of Blautia obeum (P<.05). These findings indicate that dark chocolate exerts prebiotic effects, as evidenced by its ability to restructure the diversity and abundance of intestinal bacteria; thus, it may improve negative emotional states via the gut-brain axis.
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10.
Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet.
Rej, A, Sanders, DS, Shaw, CC, Buckle, R, Trott, N, Agrawal, A, Aziz, I
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;20(12):2876-2887.e15
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Plain language summary
Irritable bowel syndrome (IBS) is a common disorder characterised by stomach pain, bloating, and altered bowel movements. Dietary therapy is a way to manage IBS, with 3 diets becoming popular amongst health care professionals and those who suffer from IBS. Traditional dietary advice (TD), which involves adopting healthy, sensible eating patterns with adequate hydration, is the first line recommendation in the UK. The low-FODMAP diet (LFD) is the avoidance of carbohydrates, which tend to ferment in the stomach and are found in certain fruits and vegetables. The gluten free diet (GFD) is the avoidance of foods which contain gluten such as bread and pasta. All three diets have little evidence to support their use in IBS and this randomised control trial of 101 individuals with IBS aimed to determine whether the GFD and LFD are superior in relieving IBS symptoms compared to TD. The results showed that GFD, LFD and TD were all effective in the management of non-constipated IBS, but that TD was easier to follow and cheaper compared to the other two diets. It was concluded that TD should be used as first-line therapy for people with non-constipated IBS and that GFD and LFD should be reserved for specific patients under the care of a health care professional.
Expert Review
Conflicts of interest:
None
Take Home Message:
- TDA, LFD and GFD can all lead to significant improvements in non-constipation IBS with no statistically significant difference in effectiveness between the diets.
- Most patients find a TDA easier and cheaper to implement than a LFD or GFD.
- TDA is therefore recommended as a first line approach in non-constipation IBS.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The aim of this study was to compare the effectiveness and patient acceptability of traditional dietary advice (TDA) vs a low FODMAP diet (LFD) vs a gluten-free diet (GFD, cross-contamination allowed) in patients with non-constipation irritable bowel syndrome (IBS).
TDA definition: healthy, sensible eating pattern, including regular meals, not eating too little/too much, adequate hydration, and reducing the intake of: alcohol/caffeine/fizzydrinks/fatty/spicy/ processed foods; fresh fruit (maximum of 3 per day); fibre/gas-producing foods and perceived food intolerances.
Methods
This was a randomised dietary trial over 4 weeks. Dietary advice was provided by a specialist dietitian in a session lasting 45-60 minutes. 99 patients completed the study (33 in each group). Stool analysis was performed in “around half“ (study authors terminology) of participants due to disruption of trial caused by COVID-19.
Results:
- Primary endpoint (reduction of 50 points or more on IBS symptom severity score) was met by 42% of patients on the TDA, 55% on LFD and 58% on GFD. The differences between groups were not statistically significant, p=0.43.
- Patients on the LFD had greater improvements in mood compared to the other diets under examination, reaching statistical significance (p=0.03) for Hospital Anxiety and Depression scale and (p<0.01) for dysphoria score on IBS-QOL scale.
- Patients on TDA found their diet cheaper (p<0.01), less time consuming to shop (p<0.01) and easier to follow when eating out with family and friends (p=0.03), whilst TDA and GFD were considered easier to incorporate into daily diet than LFD (p=0.02).
- No significant differences were found between groups in changes to macro- and micronutrient composition, except a trend to lower fibre intake with LFD (p=0.06).
- There was a significant reduction in intake of FODMAPs in all groups, with greatest reduction in LFD (27.7 to 7.6 g/day, p<0.01), followed by TDA (24.9 to 15.2 g/day, p<0.01) and GFD (27.4 to 22.4 g/day, p=0.03). Differences between groups were statistically significant (p<0.01).
- No differences were noted in change to the dysbiosis index between groups.
- Neither clinical characteristics nor dysbiosis index predicted response to any of the diets.
Conclusion
- TDA, LFD and GFD are all effective approaches for non-constipation IBS.
- TDA should be first-line dietary advice due to being the most patient-friendly.
Clinical practice applications:
- When working with clients with non-constipation IBS, a TDA approach may be favoured over LFD and GFD as a first line intervention if the patient has not already tried a TDA diet.
- Patient preferences, budget, time and living situation should be taken into account when deciding on best dietary advice for IBS.
Considerations for future research:
- As all 3 approaches led to reduction in FODMAPs, trials comparing different levels of FODMAP exclusion could lead to valuable information, as a strict FODMAP exclusion, which is commonly recommended in IBS, is difficult and may not be necessary.
- Studies of longer duration would be valuable to confirm that benefits observed with the 3 approaches are not short-term only.
- Comparing individual approaches to appropriate control group would ensure that improvements are not due to a placebo effect.
Abstract
BACKGROUND & AIMS Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD). METHODS Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination). The primary end point was clinical response after 4 weeks of dietary intervention, as defined by ≥50-point reduction in IBS symptom severity score (IBS-SSS). Secondary end points included (1) changes in individual IBS-SSS items within clinical responders, (2) acceptability and food-related quality of life with dietary therapy, (3) changes in nutritional intake, (4) alterations in stool dysbiosis index, and (5) baseline factors associated with clinical response. RESULTS The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n = 14/33) undertaking TDA, 55% (n = 18/33) for LFD, and 58% (n = 19/33) for GFD (P = .43). Responders had similar improvements in IBS-SSS items regardless of their allocated diet. Individuals found TDA cheaper (P < .01), less time-consuming to shop (P < .01), and easier to follow when eating out (P = .03) than the GFD and LFD. TDA was also easier to incorporate into daily life than the LFD (P = .02). Overall reductions in micronutrient and macronutrient intake did not significantly differ across the diets. However, the LFD group had the greatest reduction in total FODMAP content (27.7 g/day before intervention to 7.6 g/day at week 4) compared with the GFD (27.4 g/day to 22.4 g/day) and TDA (24.9 g/day to 15.2 g/day) (P < .01). Alterations in stool dysbiosis index were similar across the diets, with 22%-29% showing reduced dysbiosis, 35%-39% no change, and 35%-40% increased dysbiosis (P = .99). Baseline clinical characteristics and stool dysbiosis index did not predict response to dietary therapy. CONCLUSIONS TDA, LFD, and GFD are effective approaches in non-constipated IBS, but TDA is the most patient-friendly in terms of cost and convenience. We recommend TDA as the first-choice dietary therapy in non-constipated IBS, with LFD and GFD reserved according to specific patient preferences and specialist dietetic input. CLINICALTRIALS gov: NCT04072991.