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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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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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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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5.
Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.
Berding, K, Bastiaanssen, TFS, Moloney, GM, Boscaini, S, Strain, CR, Anesi, A, Long-Smith, C, Mattivi, F, Stanton, C, Clarke, G, et al
Molecular psychiatry. 2022
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Psychobiotic describe any exogenous intervention that leads to a bacterially mediated impact on the brain. Probiotics and prebiotics have shown promising results as psychobiotic agents in both animal and human studies. The aim of this study was to investigate the potential of a whole diet psychobiotic approach to modulate the microbiota composition and function, affect responses to and feelings of stress and improve mood in a healthy population. This study is a single-blind, randomized, controlled study which recruited healthy adult (male and female) participants with poor dietary habits, aged 18–59 years. Participants were block randomized (block of 4, stratified by gender) into either intervention or control group using randomly permuted blocks and were instructed to follow their respective diet for 4 weeks. Results show that a short term psychobiotic dietary intervention improved perceived stress in a healthy population, while eliciting specific metabolic changes in the gut microbiota. Authors conclude that underlying microbial influences need to be investigated and future preclinical experiments are required to explore causality and decipher mechanistic pathways.
Expert Review
Conflicts of interest:
None
Take Home Message:
Eating foods known to have a positive influence on gut microbial composition could elicit benefits in terms of reducing perceived stress and improving sleep quality.
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:
This RCT explored the impact of a psychobiotic diet, compared to a control diet, on perceived stress, sleep and gut microbiota.
A high psychobiotic diet is one high in prebiotic and fermented foods. In this study, a psychobiotic diet included daily recommended consumption and servings of the following:
- High prebiotic fruit & veg (6-8)
- Grains (5-8)
- Fermented foods (2-3)
- Legumes (3-4 per week)
Methodology:
- A single-blind, randomised, controlled study
- 45 healthy adults (18-59 years) with poor dietary habits
- Sample size determined by previous microbiome research - target not reached due to introduction of covid restrictrictions
- Active intervention (n=24) received dietitian advice to follow psychobitoic diet
- Control intervention (n=21) received dietitian advice largely based on the Irish Healthy Eating Guidelines food pyramid
- Intervention duration 4 weeks.
- Assessed on questionnaire measures of perceived stress and sleep, pre and post-intervention (no primary outcome defined)
- Shotgun microbiome analysis on stool samples, pre and post-intervention
Results:
- Perceived stress improved in the psychobiotic diet group
- Subjective sleep quality improved in the psychobiotic diet group
- Only subtle changes in microbial composition and function
- More stable microbiota throughout the study (regardless of diet) was correlated with greater changes in perceived stress
- Neither cortisol awakening response nor measured immune markers were affected by dietary intervention
Conclusions:
- Using a diet targeted to positively modulate gut-brain communication may have the potential for reducing stress and improving sleep
- Although improvements in stress were only observed for the intervention group – the post-intervention stress levels were not significantly different between the groups.
- Thus, we should interpret the results with some caution
Clinical practice applications:
- Providing advice on dietary intake of foods known to positively impact gut microbiota may be helpful for individuals affected by stress or sleep problems
- The inclusion of the following foods may be helpful:
- High prebiotic fruit & veg (6-8 per day)
- Grains (5-8 per day)
- Fermented foods (2-3 per day)
- Legumes (3-4 per week)
Considerations for future research:
- Important to replicate these results in a larger sample
- It might be helpful to investigate individual aspects of the diet separately, to assess their individual impact
- Objective measures of sleep (such as actigraphy recordings) might provide additionally useful findings
- It would be interesting to explore the effect of the psychobiotic diet in other conditions
- Chronobiology or chrononutrition - i.e. looking at timing of the foods proposed in the section above
Abstract
The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.
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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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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.
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7.
Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study).
Zhang, Y, Gu, Y, Ren, H, Wang, S, Zhong, H, Zhao, X, Ma, J, Gu, X, Xue, Y, Huang, S, et al
Nature communications. 2020;11(1):5015
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Berberine, which is a naturally occurring alkaloid found in plants, has been traditionally used as a remedy to protect against Type 2 diabetes and other metabolic disorders. It is important to study how berberine affects the human gut microbiome, specifically in regard to its impact on short-chain fatty acid and bile acid metabolism, due to its low oral bioavailability. The PREMOTE study investigated the glycaemic lowering effects of individual and combination of berberine and probiotics in newly diagnosed Type 2 Diabetes patients. This randomised, double-blinded, placebo-controlled trial included four hundred and nine Type 2 diabetic patients and randomly assigned them (1:1:1:1 ratio) to receive berberine alone, berberine combined with probiotics, probiotics alone or a placebo for twelve weeks. A combination of berberine plus probiotics and berberine alone significantly improved glycated haemoglobin levels compared to the placebo and probiotics alone treatment. The antidiabetic effects of berberine could be due to the Ruminococcus bromii abundance followed by the berberine treatment and its ability to inhibit deoxycholic acid biotransformation. Further robust studies are required to consider the therapeutic application of berberine and probiotics in a general population due to the limitations of the present study. However, healthcare professionals can use the results of this trial to understand the mechanism behind the anti-diabetic effects of berberine and probiotics.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The use of berberine, as a specific antimicrobial agent, along with high strength probiotics may be beneficial for managing blood glucose and potentially other metabolic health markers alongside diet and lifestyle modifications
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
Dysbiosis of the human gut microbiome has been associated with the development of type 2 diabetes (T2D). Research has found that, in part, mechanisms of action for the antidiabetic medications, Metformin and Acarbose, include alterations in the gut microbiome as well as the inhibition of bile acid (BA) metabolism and signalling. Remedies targeting the gut microbiota for treatment of T2D and other metabolic diseases have therefore been investigated.
Berberine (BBR) has been used in Indian Ayurvedic and Traditional Chinese Medicine to treat metabolic conditions for hundreds of years. Probiotics have also been extensively researched for their potential metabolic benefits. This randomised, double-blind, placebo-controlled trial aimed to investigate whether BBR and probiotics may be effective in managing T2D.
Methods
A total of 409 participants aged 42-61 years were recruited from 20 medical centres in China. All patients were newly diagnosed (<12 months) with T2D and had no previous antidiabetic medication history. Participants were randomised into 4 groups; Probiotics and BBR, BBR only, probiotics only or a placebo for 12 weeks. Subgroup analysis was also completed for those aged >50 and >54.
Dosage of BBR was 0.6 g prior to a meal, twice daily. 4 g of powdered multi-strain probiotics including 9 strains of lactic acid bacteria were taken at bedtime. All participants were given a 7-day broad-spectrum antibiotic treatment immediately prior to baseline. 391 people completed the trial. The primary outcome measurement was glycaemic haemoglobin (HbA1c). Secondary evaluations of additional metabolic markers included fasting and post-load plasma glucose (FPG, PPG), homeostasis assessment model index for insulin resistance (HOMA-IR), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and serum triglycerides (TG).
Results
Results showed a reduction in glycaemic haemoglobin (HbA1c) for both the BBR plus probiotics group (least squares mean [95% CI] -1.04 [-1-19, -0.89]% ) and the BBR only group (-.99 [-1.16, 0.83]%). The results for these groups were significantly greater than the probiotics alone (-0.53 {-068, -0.37]%) and the placebo groups (0.59 [-0.75, -0.44]%).
Secondary metabolic evaluations for FPG and PPG, TC, LDL -c and TGs also showed similar improvements in the BBR and BBR plus probiotic groups only. Additionally, in the >50 and >54 subgroups BBR and probiotics marginally improved the HOMA-IR.
Metagenomic and metabolomic analysis of the gut microbiome was also undertaken after a one-week pre-treatment with antibiotics immediately prior to the trial and at week 13. These results showed that the blood glucose lowering effects of BBR may be due to decreased deoxycholic acid species (DCA) biotransformation by ruminococcus bromii.
Higher levels of adverse gastrointestinal side effects were reported in the BBR treatment groups, however, the authors reported that this did not affect glycemic control outcomes.
Conclusion
This study found that BBR had an antidiabetic effect through microbial alterations in the human gut microbiome
The authors declare no conflicts of interest.
Clinical practice applications:
- 600mg of BBR twice daily prior to a meal plus a multi-strain (lactic acid) probiotic of >50 billion colony forming units (CFU) for 12 weeks may be effective in lowering HbA1c in T2D clients diagnosed within the previous 12 months
- Further research is needed for clients with longer term T2D diagnosis
- Insulin resistance may be marginally improved in clients >50
- Practitioners should be aware that in this study, adverse gastrointestinal side effects were more likely to be be experienced with the use of BBR
Considerations for future research:
The authors reported several limitations to this study:
- A population of Chinese people living in China may not be generalisable to other ethnic/racial populations
- The study was over a short duration. Longer studies are needed to confirm the results
- Participants had newly diagnosed T2D and had not received any previous medications. Future studies should include patients with a longer diagnosis time
- Records should be kept of any additional lifestyle changes made by the participants
- Adverse reactions were experienced in the BBR groups, in this study. It was reported that the gut microbiome and anti-diabetic effects were not affected, however, this may be something to be considered in longer trials.
Abstract
Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
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8.
Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Chahwan, B, Kwan, S, Isik, A, van Hemert, S, Burke, C, Roberts, L
Journal of affective disorders. 2019;253:317-326
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Depression is a debilitating psychiatric disorder that is the leading cause of disability world-wide. Multiple causes of depression have been identified, including genetic, neurological, inflammatory, personality, cognitive, and environmental factors. The aim of this study was to investigate the effectiveness of the multispecies probiotic Ecologic® Barrier for reducing symptoms in adults with mild to severe levels of depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial. Participants were randomly allocated into two groups; probiotic and placebo. 71 participants with depressive symptoms were recruited and allocated sequentially over 12 months. Results indicate that all participants across both probiotic and placebo groups exhibited a reduction in depressive symptoms over the time-period of the trial. Thus, the routine involved with daily preparation and consumption of the probiotic and scheduled appointments, as well as involvement in these behaviours with the aim of seeking improvement in depressive symptoms had positive impacts on mood, irrespective of whether the probiotic or placebo was consumed. Authors conclude that their findings offer evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
- The study suggests that probiotics, rather than having a direct effect on depressive symptoms, potentially act on immune system activity, inflammation and gut barrier integrity which contribute to the expression of depression.
- Probiotics may be a useful adjunct to potentiate the effects of other therapies, such as CBT.
- This study points to the validity of managing physical health as part of mental health treatment.
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:
With evidence suggesting that decreased gut barrier function and inflammation are correlated with depression, this study set out to determine the effect of consumption of probiotic supplements on depressive symptoms from a sample of 71 participants with depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial conducted over 8 weeks in Australia. Pre and post intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota were compared alongside psychological variables and gut microbiota composition to non-depressed, placebo and probiotic groups. All the clinical trial participants demonstrated an improvement in symptoms – participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group. Probiotics did not significantly alter the microbiota of depressed individuals, however a significant correlation was found between Ruminococcus gnavus and one of the metrics for depression.
Clinical practice applications:
This study was small and carried out over a short period of time. While significant results were found, which signify potential considerations for clinical practice, the results from this study do not offer evidence that the probiotics used had a direct effect on depressive symptoms – they suggest that probiotics potentially act on cognitive processes contributing to depression which may include immune system activity, inflammation, and gut barrier integrity. Overall, this study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression. In clinical practice, probiotics may be a useful adjunct to potentiate the effects of therapies, such as CBT. Finally, the use of probiotics promotes the concept of managing physical health as part of mental health treatment.
Considerations for future research:
These preliminary results are promising and offer a number of future research and clinical avenues to build upon. The results do however, indicate that a longer trial may be needed to fully assess the effects of probiotics on mood and the mechanisms by which probiotics may be influencing this. The study also suggests that further research using a range of concentrations in a dose response study may be warranted to determine the optimal dose; a greater dose over a longer period may produce detectable changes in microbiota as well as further differences in psychological data.
Abstract
BACKGROUND Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression. METHOD 71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20). RESULTS All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric. LIMITATIONS There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes. CONCLUSIONS While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.
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9.
Broccoli consumption affects the human gastrointestinal microbiota.
Kaczmarek, JL, Liu, X, Charron, CS, Novotny, JA, Jeffery, EH, Seifried, HE, Ross, SA, Miller, MJ, Swanson, KS, Holscher, HD
The Journal of nutritional biochemistry. 2019;63:27-34
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Diet affects metabolic and gastrointestinal diseases, with the microbiome considered to be a mediating factor. Broccoli is a good source of fibre and phytochemicals including glucosinolates. The aim of this investigator-blinded, controlled feeding, randomised, crossover study was to evaluate the effects of broccoli on the composition and function of the microbiome. 18 healthy adults received 200 g cooked broccoli and 20 g raw daikon radish per day for 18 days in addition to a controlled, brassica-free diet or the same diet without the broccoli and daikon radish, with a 24-day washout period. A statistically significant increase in the ratio of Bacteroidetes to Firmicutes was observed following the broccoli intervention. When stratified by BMI above or below 25, this increase was only seen in those with a lower BMI whilst those with a higher BMI displayed a decrease in the ratio, although the latter was not statistically significant. In those with the lower BMI, there was also a correlation between the changes in the microbiota composition and glucosinolate metabolites. It was predicted that the involved changes would affect the functions of the endocrine system, transport and catabolism and energy metabolism. The authors concluded that eating broccoli may affect both the composition and the function of the microbiome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Broccoli consumption at dosages of 200g per day were shown to change the composition of gastrointestinal microbiota, increasing Bacteroidetes and decreasing Firmicutes, and impact their function
- The observed results were strongest in those with a BMI of less than 26
- While interesting, the study only included 18 participants and therefore the results should be further confirmed.
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
There is growing evidence linking dysbiosis of the gastrointestinal microbiota and diet-induced gastrointestinal and metabolic diseases. Both long-term and acute dietary changes, fasting, eating frequency, and consumption of specific fibres and food phytochemicals play a role in shaping the composition and function of the microbiota, although evidence is lacking for specific foods. This study aimed to determine the impact of broccoli intake on the number of bacterial strains and their functional capacity.
Methods
This was a single-blind, randomised, crossover, complete feeding intervention. Study participants were healthy adults (n=18, females =10). Participants were requested to not eat Brassica vegetables for 3 weeks before the start of the study.
Subjects participated in two 18-day diet periods separated by a 24-hour washout, during which breakfast and dinner were consumed on site to observe compliance. The control diet was prepared using traditional American foods, excluding all Brassica vegetables. During the broccoli intervention period, participants consumed the same base diet with the addition of 200g of broccoli.
Faecal samples were collected on day 1, and day 16. Quantitative polymerase chain reaction was performed on bacterial strains. On day 17, time series plasma sampling and 24-hour urine collection was done.
Results
There was no difference in alpha diversity (a measure of microbiome diversity within a sample) between the two treatment periods. This indicates that no bacterial species were extinguished by broccoli treatment. Beta diversity analysis (a measure of the (dis)similarity between samples) indicated that bacterial communities were impacted by treatment (P=0.03).
After broccoli consumption, Bacteroidetes increased by 10% (P =0.03), while Firmicutes decreased by 8% (P=0.05). Overall the ratio of Bacteroidetes to Firmicutes increased by 37% (P=0.01) versus a 5% decrease in the control period. The Bacteroides genus increased by 6% (P=0.02) versus a 2% decrease in the control period.
Interestingly, the effects were most strong in those with a lower BMI (< 26 kg/m2) who had an increase in metabolites after broccoli consumption. Algorithms to predict the function of the microbiota showed that broccoli increased endocrine (P=0.05), energy metabolism (P=0.01), transport and catabolism (P=0.04) pathways.
Conclusion
Broccoli intake, at 200g daily, changes the composition and potentially impacts the function of the gut microbiota.
Clinical practice applications:
- Studies like this allow practitioners to focus on specific foods in specific quantities to positively alter the microbiota and their function
- Cruciferous vegetables, like broccoli, kale, cauliflower, cabbage, Brussel sprouts, are an important group as they contain fibre and phytonutrients such as glucosinolates. These compounds can be metabolised by the microbiota into active compounds with health benefits. This study has shown the bidirectional benefit of broccoli consumption in that it can positively impact the function and composition of the microbiota
- Interestingly, the results in this small study were driven by participants with a BMI of less than 26. Sub-group analysis found no statistically significant relationships in participants with BMI >26
- It is worth noting that it is possible that the addition of 5g of fibre from the broccoli is also contributing to the changes observed.
Considerations for future research:
- Larger, controlled feeding studies that isolate specific foods to identify their effects on the microbiota are needed
- Genetic sequencing for only a few bacterial myrosinases has been completed and therefore future studies should aim to assess the metabolic capabilities in faecal samples such as myrosinase activity
- While this study and others have shown changes in the types of bacteria after cruciferous vegetable consumption the consistency of results has been mixed potentially due to differing study designs and treatment dosages. Further studies to clarify and confirm these results would be beneficial
- To assess the function of the microbiota a predictive algorithm was used. This requires experimental confirmation by such methods as metabolite profiling and whole genome shotgun sequencing.
Abstract
The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.