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Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial.
Medawar, E, Beyer, F, Thieleking, R, Haange, SB, Rolle-Kampczyk, U, Reinicke, M, Chakaroun, R, von Bergen, M, Stumvoll, M, Villringer, A, et al
Gut. 2024;73(2):298-310
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It is thought that there is a connection between the gut microbiota and the brain and that prebiotics which fuel these gut microbiota may be able to affect mood and decision making. This randomised control trial of 59 individuals with overweight aimed to determine if supplementation of prebiotic fibre in the form of inulin could affect the desire for food. The results showed that compared to placebo individuals given inulin had a lower desire towards high caloric foods in conjunction with a change in the composition of the gut microbiota, especially Bifidobacteriaceae. It was concluded that prebiotics may be able to alter food-related decision making and alter the composition of the gut microbiota. This study could be used by healthcare professionals to understand that individuals who are overweight may choose unhealthy foods due to an imbalance in their gut microbiota. These individuals may benefit from prebiotic fibre to help aid microbiota changes and empowerment over food choices.
Abstract
OBJECTIVE Animal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fibre on reward-related food decision-making in a randomised controlled within-subject cross-over study and assayed potential microbial and metabolic markers. DESIGN 59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/day of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool. RESULTS Compared with placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (preregistered, family wise error-corrected p <0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producing Bifidobacteriaceae, and changes in >60 predicted functional signalling pathways after prebiotic intake. Changes in brain activation correlated with changes in Actinobacteria microbial abundance and associated activity previously linked with SCFA production, such as ABC transporter metabolism. CONCLUSIONS In this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food decision-making, paralleled by shifts in gut microbiota. TRIAL REGISTRATION NUMBER NCT03829189.
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Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.
Prokopidis, K, Giannos, P, Kirwan, R, Ispoglou, T, Galli, F, Witard, OC, Triantafyllidis, KK, Kechagias, KS, Morwani-Mangnani, J, Ticinesi, A, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(1):30-44
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Sarcopenia is a progressive skeletal muscle disorder involving accelerated loss of muscle mass, strength and function. It generally occurs in older age groups but can also be seen in younger people. Multiple factors contribute to the development of the condition. Besides nutritional management strategies, probiotics have recently caught the interest of researchers. As probiotics promote metabolic building activity, aid digestion and absorption and reduce muscle breakdown by favourably managing inflammation, they present great potential for the management of sarcopenia. This systematic review and meta-analysis explored the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. The review included 24 studies, with probiotics mainly from the Bifidobacteria or Lactobacilli family. The analysis concluded that probiotic supplementation improved muscle mass in comparison to placebos. It also significantly increased overall muscle strength in 6 randomized controlled trials, which was most obvious in age groups of 50 and above. However, no changes were seen concerning total lean mass. It appeared that longer studies, of >12 weeks or more, showed better outcomes in this review. Furthermore, Bifidobacteria species seemed to exhibit more favourable effects, and the authors also noted the beneficial results were more significant in Asian populations. Further research is needed to understand more about the underlying mechanism, best probiotics strains and the specifics of different demographic groups. This article yields a concise overview of sarcopenia, the nutritional aspects of the disease and how probiotics may be beneficial in disease management, strengthened with data from the review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This was a well-conducted meta-analysis based on its methodological approach that demonstrated that Lactobacillus and Bifidobacterium probiotic supplementation may contribute to improved muscle mass in younger adults and improved muscle strength in older adults.
- Bifidobacterium probiotic supplementation was associated with enhanced muscle mass in younger adults, a potential focus for those considering probiotic supplements.
- The duration of probiotic therapy matters, with longer-term (12 weeks or more) supplementation showing improvements in muscle mass and strength..
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 systematic review and meta-analysis evaluated the effect of probiotics on muscle mass, total lean mass and muscle strength in both young and older adults.
Methods
- The search encompassed PubMed, Scopus, Web of Science, and Cochrane Library databases, from inception up to June 2022; studies included spanned a period from 2013 to June 2022.
- The study adhered to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines and included the Risk-of-Bias tool to assess study quality.
- The study focused on changes in muscle mass, total lean mass, and muscle strength.
- Inclusion criteria: randomised controlled trials (RCTs) with adult participants (>18 years); interventions involving any probiotics, and a control group receiving either no treatment or a placebo.
Results
- 24 RCTs were included (709 participants), with studies conducted in Europe, USA, and Asia. Intervention durations: ranged from 3 weeks to 12 months.
- Participants included overweight, untrained healthy and resistance-trained individuals, and those with specific conditions like metabolic syndrome and frailty.
- Body composition assessments were conducted using bioelectrical impedance (BIA) and/or dual-energy X-ray absorptiometry (DXA).
- Probiotic strains employed in the included studies varied, with Lactobacillus the most common, followed by Bifidobacterium; some combined both. 5 of 24 studies also used additional strains.
- Dosages: ranged from 2 × 10^9 to 11.2 × 10^10 colony-forming units (CFU).
- 4 out of 24 studies used fermented food products like cheese and noodles as sources of probiotics.
- 22 RCTs measured muscle mass and total lean mass; 6 RCTs measured global muscle strength.
- Probiotic supplementation (≥12 weeks) moderately increased muscle mass, with a standardised mean difference (SMD) of 0.42. This significant effect (95% CI: 0.10–0.74, P=0.009) was observed only in younger Asian adults (<50 years) after Bifidobacterium supplementation, based on a meta-analysis of 10 studies.
- Probiotic supplementation (≥12 weeks) significantly increased global muscle strength in older adults (>50 years; SMD: 0.69, 95% CI: 0.33–1.06, P = 0.0002).
- Probiotic supplementation showed no significant impact on lean mass (SMD: -0.03, 95% CI: 0.19 – 0.13, P = 0.69).
Conclusion
Probiotic supplementation, especially Lactobacillus and Bifidobacterium may have a positive impact on muscle mass and global strength
Clinical practice applications:
- Consumption of probiotics, mainly Lactobacillus and Bifidobacterium may contribute to improved muscle strength in older individuals (>50y).
- Consumption of Bifidobacterium strains was associated with improved muscle mass in younger individuals (<50y) in Asian countries, in a low number of studies (k=2).
- Bifidobacterium breve B-3 was associated with an improvement in muscle mass in older overweight individuals, although a causal relationship was not established.
- Probiotics may enhance muscle mass or strength by enhancing protein digestion and amino acid absorption for muscle synthesis and function.
- Considering an individual’s goals, a practitioner could consider probiotic supplementation as a complementary intervention when aiming to enhance muscle mass or strength .
Considerations for future research:
- Future research could focus on pinpointing which specific probiotic strains are most effective for muscle strength or muscle mass to tailor more precise interventions.
- Most studies did not exceed 12 weeks, highlighting the need for long-term research on probiotics sustained muscle impact.
- Future research could investigate the effects of probiotics across diverse demographic groups including different ages, sexes, and ethnic backgrounds to understand the impact in different populations.
- Delving deeper into the mechanisms by which probiotics influence muscle health could lead to targeted probiotic therapies that address specific physiological pathways.
- Finally, future research could explore how probiotics can be combined with other interventions, such as exercise or nutritional modifications, to synergistically improve muscle health and function.
Abstract
Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2 = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2 = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2 = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.
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The effect of synbiotic supplementation on hypothyroidism: A randomized double-blind placebo controlled clinical trial.
Ramezani, M, Reisian, M, Sajadi Hezaveh, Z
PloS one. 2023;18(2):e0277213
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Despite the increased awareness and the improvements in medical management of hypothyroidism; depression, mood disturbance and poor health-related quality of life (QoL) is common among hypothyroid patients. Synbiotics have been advocated as being beneficial to patients with metabolic diseases. Synbiotics are a mixture of probiotics and prebiotics that beneficially affect the host by improving the survival and stimulating the growth of advantageous and health promoting microbial species in the gastrointestinal tract. The aim of this study was to examine whether synbiotic supplementation could enhance depression, QoL, and blood pressure, as well as thyroid hormones in hypothyroid patients. This study is a 10-week parallel design randomised placebo-controlled trial. Participants – adults with hypothyroidism - were randomly assigned to the synbiotic (n = 28) or the placebo (n = 28) group. Results show that following 10 weeks supplementation with synbiotics (500 mg of 10⁹ CFU/g probiotics plus fructo-oligosaccharide) in comparison to placebo does not affect serum thyroid stimulating hormone level and depression. However, it significantly improved blood pressure levels and various domains and areas of QoL. Authors conclude that further clinical trials are needed to assess the effectiveness of a synbiotic supplementation along with the current routine treatment for hypothyroid patients.
Abstract
OBJECTIVE We hypothesize that synbiotic supplementation could modulate the intestinal microbiota and subsequently, improve the condition of hypothyroid patients. METHODS Fifty-six adult hypothyroid patients were recruited to this double-blind, placebo-controlled, randomized clinical trial. The intervention was 10 weeks of synbiotic (500 mg of 109 CFU/g probiotics plus fructo-oligosaccharide, n = 28) compared to placebo (lactose, magnesium stearate, talc, and silicon dioxide, n = 28). Randomization and allocation to trial groups were carried out using random number sequences drawn from https://sealedenvelope.com/. Primary outcomes were serum thyroid stimulating hormone (TSH) and free thyroxine (FT4), and secondary outcomes were depression, quality of life, and blood pressure (BP). P-values< 0.05 were considered statistically significant. RESULTS Analysis on 51 patients who completed the trial showed that TSH and depression (p> 0.05) did not change significantly, while serum FT4 significantly increased in both groups (p = 0.03 and p = 0.02 in symbiotic and placebo respectively). A significant decrease in systolic BP occurred only in the synbiotic group (p = 0.05). Significant improvements occurred regarding different domains and areas of quality of life in the crude and adjusted analysis, including perceived mental health (p = 0.02), bodily pain (p = 0.02), general health perception (p = 0.002), and wellbeing (p = 0.002), which were significantly higher in the synbiotic group. CONCLUSIONS Ten-week supplementation with synbiotic had no favorable effect on depression and TSH, but it improved blood pressure and quality of life in patients with hypothyroidism. More trials are needed to support or reject these findings. TRIAL REGISTRATION IRCT20210926052583N1, Iranian Registry of Clinical Trials (IRCT), registered October 1st, 2021.
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Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.
Yang, LL, Stiernborg, M, Skott, E, Xu, J, Wu, Y, Landberg, R, Arefin, S, Kublickiene, K, Millischer, V, Nilsson, IAK, et al
Nutrients. 2023;15(5)
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Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental psychiatric disorder. The core symptoms of the disorder are inattention and hyperactivity/impulsivity. The aim of this study was to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and short-chain fatty acids (SCFAs) in ADHD. This study is a double-blind randomised controlled trial over a period of 9-weeks. Patients (n= 248) were randomly allocated to one of the two treatments: Synbiotic 2000 or placebo. Results show that there was no statistically significant overall effect of Synbiotic 2000 compared to placebo on any analyte analysing all the paediatric and all adult participants as one group. However, age-group stratified analyses showed that plasma levels of several of the analytes were at baseline different in the children compared to in the adults. Authors conclude that Synbiotic 2000, in children with ADHD, reduces markers of intestinal and vascular inflammation, the latter in part through increasing SCFAs levels. Furthermore, they suggest that the findings warrant further studies to determine if persons with ADHD would benefit inflammation-wise from dietary intake of Synbiotic 2000 or a similar synbiotic.
Abstract
Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.
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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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Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults.
Haskell-Ramsay, CF, Dodd, FL, Smith, D, Cuthbertson, L, Nelson, A, Lodge, JK, Jackson, PA
The Journal of nutrition. 2023;152(12):2778-2788
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Cognitive impairment is a growing worldwide health concern as our population ages. In the absence of effective pharmaceutical treatments, modifiable lifestyle factors such as nutrition represent crucial targets in preventing cognitive decline. The aim of this study was to investigate the cognitive and mood effects of mixed tree nut supplementation in healthy non-elderly adults aged 18 to 49 years. This study is a randomised, placebo-controlled, double-blind, counterbalanced crossover design. Participants (n = 81) were randomly assigned to one of the two groups; the treatment or placebo group. Results showed that nut consumption led to improved picture recognition in terms of increased accuracy and faster reaction time. Furthermore, there was an enrichment of an unclassified type of bacterial community (Lachnospiraceae) but limited changes to the urinary metabolome. On the other hand, supplementation with mixed nuts failed to evince effects on mood. Authors conclude by pointing out that their findings are attributed to a sample of healthy and nonelderly participants. Thus, more profound effects may be shown with higher quantities of nuts or in those at risk, such as those experiencing cognitive decline or in those suffering gut dysbiosis.
Abstract
BACKGROUND Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study. OBJECTIVES The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults. METHODS This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2). RESULTS Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or β diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome. CONCLUSIONS These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.
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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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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This randomised controlled intervention study compared gut health parameters with the use of a synbiotic pre- and probiotic strain enriched infant formula with human milk and standard formula at three intervals over a period of 2 years.
Methods
This was a double-blinded controlled study of 540 infants from France and Belgium. Participants were randomly allocated to 2 formula groups (n = 230 Control Formula (CF), n = 230 Intervention Formula (IF)) and the breastfed reference group (n = 80) as well as delivery mode (Cesarean and vaginal delivery). The synbiotic IF was a standard infant formula enriched with prebiotic GOS (0.02 g/g) and the probiotic strain L. fermentum CECT5716 (at least 1.0 × 106 cfu/g).
Stool analysis was conducted at three time intervals, 4, 12, and 24 months (infant age). Biomarkers included short chain fatty acids, pH, secretory IgA, calprotectin, and various bacterial phyla via microbiota analysis.
Results
- At 4 months, the IF group tested higher for Bifidobacterium spp., and Lactobacillaceae and lower occurrence of Blautia spp., as well as Ruminoccocus gnavus and relatives compared to CF. They also had lower fecal pH and butyrate levels
- Both the formula cohorts had lower SigA and more basic pH values than the human milk cohort, as well as higher prevalence of anaerobes belonging to the bacterial genera Akkermansia, Collinsella, and Faecalibacterium.
- By age 24 months, the IF cohort exhibited increased levels of Akkermansia, Escherichia-Shigella, and R.gnavus. However there were no significant differences between the formula fed and human milk cohort at this time interval.
- The differences observed at 4 months disappeared over time, except for a significantly higher relative abundance of bifidobacteria and Faecalibacterium spp. in IF infants at 12 months compared with CF infants.
Conclusion:
Although prominent differences between the cohorts were observed at 4 months, it appears that by the age of 2 years, there is little observable difference. This is most likely due to gut ecosystem maturation. The paper draws attention to the fact that changes to microbiota following treatment were more pronounced in infants who tested lower in occurrences of Bacteroides spp at age 4 months. Of note is the prevalence of cesarean birth deliveries in this cohort thereby indicating potential improved alternative feeding options when breastfeeding is not possible for these infants.
Clinical practice applications:
- Probiotic L.fermentum and prebiotic galacto-oligosaccharide enriched infant formula appears to the improve infant microbiome, when compared to that of breastfed infants.
- The most receptive infants were those born via cesarean section.
Limitations to consider:
- The sample groups were from France and Belgium, with no indication as to culture, socio-economic, or sex distribution.
- The two infant formula groups were n=230 each with only 80 infants in the breastfed reference group.
- There was no indication of maternal diet practices pre-, during, and post- pregnancy.
- Stool samples were not collected from the infants at baseline visit prior to formula intervention.
Considerations for future research:
- Future studies need to include more diverse cultural and socio-economic cohorts to ascertain the potential influence of parental diet in baseline infant microbiome.
- It is imperative to establish what role solid food choices, generally introduced at 6 months, might have on gut ecosystem maturation.
- It would be useful to have a larger cesarean section birth cohort to compare to vaginal deliveries for more definitive results.
Abstract
BACKGROUND Microbial colonization of the gastrointestinal tract after birth is an essential event that influences infant health with life-long consequences. Therefore, it is important to investigate strategies to positively modulate colonization in early life. OBJECTIVES This randomized, controlled intervention study included 540 infants to investigate the effects of a synbiotic intervention formula (IF) containing Limosilactobacillus fermentum CECT5716 and galacto-oligosaccharides on the fecal microbiome. METHODS The fecal microbiota from infants was analyzed by 16S rRNA amplicon sequencing at 4, 12, and 24 months of age. Metabolites (e.g., short-chain fatty acids) and other milieu parameters (e.g., pH, humidity, and IgA) were also measured in stool samples. RESULTS Microbiota profiles changed with age, with major differences in diversity and composition. Significant effects of the synbiotic IF compared with control formula (CF) were visible at month 4, including higher occurrence of Bifidobacterium spp. and Lactobacillaceae and lower occurrence of Blautia spp., as well as Ruminoccocus gnavus and relatives. This was accompanied by lower fecal pH and concentrations of butyrate. After de novo clustering at 4 months of age, overall phylogenetic profiles of the infants receiving IF were closer to reference profiles of those fed with human milk than infants fed CF. The changes owing to IF were associated with fecal microbiota states characterized by lower occurrence of Bacteroides compared with higher levels of Firmicutes (valid name Bacillota), Proteobacteria (valid name Pseudomonadota), and Bifidobacterium at 4 months of age. These microbiota states were linked to higher prevalence of infants born by Cesarean section. CONCLUSIONS The synbiotic intervention influenced fecal microbiota and milieu parameters at an early age depending on the overall microbiota profiles of the infants, sharing a few similarities with breastfed infants. This trial was registered at clinicaltrials.gov as NCT02221687.
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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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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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Plain language summary
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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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.