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Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial.
Schneider, E, Doll, JPK, Schweinfurth, N, Kettelhack, C, Schaub, AC, Yamanbaeva, G, Varghese, N, Mählmann, L, Brand, S, Eckert, A, et al
Journal of psychiatry & neuroscience : JPN. 2023;48(1):E23-E33
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Major depressive disorder (MDD) is often thought of as being solely a mood disorder. However, several studies have shown that sufferers can also experience decreased brain function such as memory loss and poor attention. Current therapies for MDD focus on the balancing of mood and leaves the problem of reduced brain function unattended. The gut microbiota has recently been shown to influence brain function and altered gut microbiota composition has been seen in individuals with MDD. Targeting the gut microbiota may therefore represent a novel target for MDD treatments. This secondary analysis of a randomised control trial aimed to determine whether a probiotic multistrain supplement could improve brain function in 60 individuals with depression. The results showed that probiotics improved the brain function in two different ways, the immediate recall of words, and the improvement of decreased neural function in the hippocampal part of the brain, which has been associated with MDD. It was concluded that probiotic supplementation can enhance verbal episodic memory and improve neural function associated with impaired brain function in MDD. This study could be used by healthcare professionals to understand that the health of the gut microbiota can have an influence on brain function and that probiotics may help individuals with MDD who are suffering from poorer memory.
Abstract
BACKGROUND In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression. METHODS This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention. RESULTS We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes. LIMITATIONS The modest sample size resulting from our exclusion of low-compliant cases should be considered. CONCLUSION Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression. CLINICAL TRIAL REGISTRATION clinicaltrials.gov identifier NCT02957591.
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Probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: The PPDP follow-on study.
Yan, Q, Hu, W, Tian, Y, Li, X, Yu, Y, Li, X, Feng, B
Frontiers in endocrinology. 2023;14:1113611
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Compared with normal glucose tolerance, people with prediabetes, especially impaired glucose tolerance (IGT), have a higher risk of developing type 2 diabetes mellitus (T2DM). Early intervention can significantly reduce the probability of developing T2DM in the IGT population. The aim of this study was to observe the effect of early probiotic intervention on the conversion of T2DM after 6 years. This study was a follow-on study of the Probiotics Prevention Diabetes Program (PPDP) Study. A total of 39 non-T2DM patients agreed to continue with the follow up of glucose metabolism for the following 4 years. Results showed that supplementation with active probiotics of Bifidobacterium, Lactobacillus acidophilus and Enterococcus faecalis is safe, although it does not reduce the risk of IGT conversion to diabetes mellitus. Authors conclude that more clinical and laboratory studies using large samples and long-term observation are needed to explore the effects of different probiotic strains on IGT.
Abstract
OBJECTIVES The purpose of this study was to assess the incidence of type 2 diabetes mellitus (T2DM) after 6 years in patients with IGT who received early probiotic intervention in the Probiotics Prevention Diabetes Program (PPDP) trial. METHODS 77 patients with IGT in the PPDP trial were randomized to either probiotic or placebo. After the completion of the trial, 39 non-T2DM patients were invited to follow up glucose metabolism after the next 4 years. The incidence of T2DM in each group was assessed using Kaplan-Meier analysis. The 16S rDNA sequencing technology was used to analyze gut microbiota's structural composition and abundance changes between the groups. RESULTS The cumulative incidence of T2DM was 59.1% with probiotic treatment versus 54.5% with placebo within 6 years, there was no significant difference in the risk of developing T2DM between the two groups (P=0.674). CONCLUSIONS Supplemental probiotic therapy does not reduce the risk of IGT conversion to T2DM. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/showproj.aspx?proj=5543, identifier ChiCTR-TRC-13004024.
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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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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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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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Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial.
Takeda, T, Asaoka, D, Nojiri, S, Yanagisawa, N, Nishizaki, Y, Osada, T, Koido, S, Nagahara, A, Katsumata, N, Odamaki, T, et al
The American journal of gastroenterology. 2023;118(3):561-568
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Chronic constipation is one of the main obstacles to healthy longevity. In recent years, reports using next-generation sequencing have shown that the amount of bifidobacteria is reduced in the stools of elderly individuals. The relationship between chronic constipation and gut microbiota has attracted attention. The aim of this study was to investigate the effects of Bifidobacterium longum (BB536) on constipation and abdominal symptoms in elderly patients with chronic constipation. This study is a double-blind, randomised, controlled trial with two arms. Participants (n=80) were randomly assigned to the probiotic (n=39) or placebo (control n=41) group. Each participant consumed 1 probiotic or placebo sachet daily for 4 weeks and was asked to participate in 4 weeks of post-observation. Results show an improvement in the patients’ bowel movements and upper abdominal symptoms after 4 weeks of BB536 intake compared with the placebo group. Furthermore, some of the improved symptoms were maintained even 4 weeks after stopping the probiotics. Authors conclude that the probiotic therapy used in their study had very few adverse effects suggesting the safety and usefulness of taking BB536 for chronic constipation in elderly individuals.
Abstract
INTRODUCTION Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation. METHODS This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics ( B. longum BB536, 5 × 10 10 colony-forming unit, n = 39) or placebo (n = 41) once daily for up to 4 weeks. The severity of constipation was evaluated using the Constipation Scoring System. The primary end point was the difference in the changes from baseline in the constipation scoring system total score between the 2 groups at week 4. RESULTS A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary end point was not significant ( P = 0.074), although there was significant improvement ( P < 0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the stool frequency ( P = 0.008) and failure of evacuation ( P = 0.051) subscales, respectively, at week 4 between the 2 groups. Few adverse events related to the probiotics were observed. DISCUSSION The primary end points were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals.
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The effect of a preconception and antenatal nutritional supplement on children's BMI and weight gain over the first 2 years of life: findings from the NiPPeR randomised controlled trial.
Lyons-Reid, J, Derraik, JGB, Kenealy, T, Albert, BB, Nieves, JMR, Monnard, CR, Titcombe, P, Nield, H, Barton, SJ, El-Heis, S, et al
The Lancet. Global health. 2023;11 Suppl 1:S11-S12
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Rapid weight gain in infancy is associated with future adverse metabolic health. Nutrition intervention before and during pregnancy may promote healthy weight gain in infants, however evidence is lacking. The purpose of this study was to see whether preconception and antenatal supplementation effects the size and growth of children from birth until 2 years of age. 1729 women were recruited for the study and divided into two groups. The intervention group took myo-inositol, probiotics and additional micronutrients, the control group took a standard micronutrient supplement. Measurements of weight and length were obtained from 576 children at multiple intervals during the first 2 years of life. Differences in age and sex standardised BMI at age 2 years (WHO standards) and the change in weight from birth were examined. The results show that the infants where the mother took the intervention supplement before and throughout pregnancy had a lower risk of rapid weight gain and high BMI at age 2 years. Long-term follow-up is required to assess the longevity of these benefits.
Abstract
BACKGROUND Nutritional intervention before and throughout pregnancy might promote healthy infant weight gain; however, clinical evidence is scarce. Therefore, we examined whether preconception and antenatal supplementation would affect the body size and growth of children in the first 2 years of life. METHODS Women were recruited from the community before conception in the UK, Singapore, and New Zealand, and randomly allocated to either the intervention (myo-inositol, probiotics, and additional micronutrients) or control group (standard micronutrient supplement) with stratification by site and ethnicity. Measurements of weight and length were obtained from 576 children at multiple timepoints in the first 2 years of life. Differences in age and sex standardised BMI at age 2 years (WHO standards) and the change in weight from birth were examined. Written informed consent was obtained from the mothers, and ethics approval was granted by local committees. The NiPPeR trial was registered with ClinicalTrials.gov (NCT02509988) on July 16, 2015 (Universal Trial Number U1111-1171-8056). FINDINGS 1729 women were recruited between Aug 3, 2015, and May 31, 2017. Of the women randomised, 586 had births at 24 weeks or more of gestation between April, 2016, and January, 2019. At age 2 years, adjusting for study site, infant sex, parity, maternal smoking, maternal prepregnancy BMI, and gestational age, fewer children of mothers who received the intervention had a BMI of more than the 95th percentile (22 [9%] of 239 vs 44 [18%] of 245, adjusted risk ratio 0·51, 95% CI 0·31-0·82, p=0·006). Longitudinal data revealed that the children of mothers who received the intervention had a 24% reduced risk of experiencing rapid weight gain of more than 0·67 SD in the first year of life (58 [21·9%] of 265 vs 80 [31·1%] of 257, adjusted risk ratio 0·76, 95% CI 0·58-1·00, p=0·047). Risk was likewise decreased for sustained weight gain of more than 1·34 SD in the first 2 years (19 [7·7%] of 246 vs 43 [17·1%] of 251, adjusted risk ratio 0·55, 95% CI 0·34-0·88, p=0·014). INTERPRETATION Rapid weight gain in infancy is associated with future adverse metabolic health. The intervention supplement taken before and throughout pregnancy was associated with lower risk of rapid weight gain and high BMI at age 2 years among children. Long-term follow-up is required to assess the longevity of these benefits. FUNDING National Institute for Health Research; New Zealand Ministry of Business, Innovation and Employment; Société Des Produits Nestlé; UK Medical Research Council; Singapore National Research Foundation; National University of Singapore and the Agency of Science, Technology and Research; and Gravida.
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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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Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.
Wastyk, HC, Perelman, D, Topf, M, Fragiadakis, GK, Robinson, JL, Sonnenburg, JL, Gardner, CD, Sonnenburg, ED
Gut microbes. 2023;15(1):2178794
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Rates of metabolic syndrome are high throughout developed countries. Metabolic syndrome is a cluster of conditions that occur together and increase your risk for heart disease, stroke, and type 2 diabetes. Studies in animals and humans have shown that the composition of the gut microbiome may be linked to metabolic syndrome and that it is affected by diet. This randomised control trial of 39 individuals showed that the supplementation of a probiotic containing three different probiotic strains did not have a population wide effect but did influence a subset of individuals. These individuals had a different microbiome by the end of the trial and a decrease in blood pressure and blood lipids. Interestingly these individuals also had a higher dietary intake of sugar, yet a lower blood sugar level. It was concluded that the response to probiotic supplements may be dependent upon an individual’s diet. This study could be used by healthcare professionals to understand that diet may influence the success of probiotics, however more research is warranted before firm conclusions are made on the optimal diet during supplementation.
Abstract
An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism.
Zhu, R, Fang, Y, Li, H, Liu, Y, Wei, J, Zhang, S, Wang, L, Fan, R, Wang, L, Li, S, et al
Frontiers in immunology. 2023;14:1158137
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Test anxiety, characterised by feelings of failure, tension, and worrying when an individual faces a vital test for promoting, occurs prevalently among college students. Lactobacillus plantarum, has become increasingly popular in reducing the severity of anxiety and depression in stressed animal models. The main aim of this study was to evaluate the psychological effects of Lactobacillus plantarum JYLP-326 (JYLP-326) on exam stress-induced behaviours like anxiety, depression, and insomnia. This study enrolled 60 anxious and 30 un-anxious undergraduates preparing for the approaching exams. Out of the 60 anxious participants, 30 were selected randomly to receive the probiotic product and the other 30 received a placebo product. The 30 un-anxious students were assigned as the healthy control group. Results demonstrated that the intervention of JYLP-326 is effective in alleviating exam stress-induced symptoms in college students. Furthermore, it also protected against exam stress-induced dysbiosis of the gut microbiota and the disturbances of faecal metabolomic. Authors conclude that the changed gut microbiota genera and faecal metabolites were closely associated with stress-related symptoms like anxiety/depression and insomnia, indicating that they might be regarded as biomarkers for diagnosing and treating stress and anxiety disorders.
Abstract
INTRODUCTION Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students. METHODS Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism. RESULTS The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms. CONCLUSION The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.