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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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Plain language summary
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 Gut Microbiome in Early Life Stress: A Systematic Review.
Agusti, A, Lamers, F, Tamayo, M, Benito-Amat, C, Molina-Mendoza, GV, Penninx, BWJH, Sanz, Y
Nutrients. 2023;15(11)
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Children exposed to early life stress (ELS) show alterations in brain development and are at increased risk of developing mental illness. This study aims to clarify whether ELS influences the gut microbiome and whether this can be a predictor for the development of mental disorders. 13 articles were included in this systemic review. 4 looked at pre-natal stress and 9 at post-natal stress. Prenatal stress (via maternal stress) may be associated with an increase in Proteobacteria phylum and with a lower abundance of Bifidobacterium and lactic acid bacteria. In the postnatal group, greater microbiome diversity was related to lower depression and anxiety. In boys scores for adaptive skills were higher in those with good levels of Bifidobacterium. A positive association was found between EA (early adversity) experiences and gastrointestinal symptoms and anxiety. This review demonstrates links between ELS and gut microbiome changes. Further research will be necessary to draw more robust conclusions.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review consolidated and discussed existing evidence on the link between early life stress (ELS) and changes to the human microbiome
- Exposure to ELS, prenatal or postnatal during childhood and adolescence, may impact mental and physical health.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A systematic review was conducted to consolidate clinical evidence examining the impact of early life stress (ELS) on the human intestinal microbiome.
Method
Thirteen observational studies were included in the review, sourced from Pubmed, Scopus, Web of Science, and EMBASE. Methodological quality was assessed using the Newcastle-Ottawa Assessment Scale (NOS), with most studies scoring seven or eight out of nine stars.
Study designs varied, including prospective prenatal studies, postnatal longitudinal studies, case-control studies, and cross-sectional studies. Four prenatal studies were prospective in design. The other nine postnatal studies included one longitudinal study, five case-control studies, and three cross-sectional studies. All 13 studies were published between 2015 and 2022. Because study designs and outcome assessments varied, the results were presented in a narrative form. Data was extracted by 2 independent authors.
Results
The primary findings from the review were as follows:
- Four longitudinal stress studies indicated that pregnant mothers experiencing psychological stress, increased cortisol levels, HIV, and lack of social support exhibited a lower abundance of beneficial Bifidobacterium and an increased abundance of Enterobacter genus.
- One postnatal stress longitudinal study (n=260) demonstrated lower depression and anxiety and improved internalising behaviour in patients with high microbiome diversity.
- . One postnatal stress case-control study (n=344) showed changes in the microbiome and an abundance of several bacterial taxa in stressed groups, including genera Prevotella, Bacteroides (Bacteroidetes), Coprococcus, Streptococcus, and Escherichia.
- One cross-sectional study of 128 adults without psychiatric conditions revealed that higher stress correlated with increased levels of Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter, and Roseburia at the genus level, as well as lower Phascolarcto bacterium and Firmicutes at the phylum level.
- One large prospective study (n=446) found infants exposed to higher cumulative stress exhibited an increased relative abundance of Proteobacteria groups and lower Bifidobacterium.
Conclusion:
Due to the inconsistency of study designs and their results this review failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both.
Clinical practice applications:
- Early life stress, and alterations in the gut microbiome, have been linked to mental health conditions
- Maternal prenatal stress may be linked to emotional, behavioural, and cognitive outcomes in infants.
Considerations for future research:
- Future research should standardise questionnaires, to ensure consistency and comparability across studies
- Additionally, future studies should consider using standard procedures and specific species and strain resolution shotgun metagenomics sequencing
- Consideration should be given to the influence of environmental variables (diet, physical activity, etc.) and sex in gut microbiome analysis.
Abstract
Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.
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The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.
Naseri, K, Saadati, S, Ghaemi, F, Ashtary-Larky, D, Asbaghi, O, Sadeghi, A, Afrisham, R, de Courten, B
European journal of nutrition. 2023;62(2):543-561
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When acute, inflammation is a necessary function of the immune system allowing the body to recognise and remove foreign stimuli. However, when chronic inflammation occurs, it can contribute to and exacerbate diseases such as type 2 diabetes (T2D). The gut microbiota and the use of probiotics has been shown to modulate processes within the body and decrease chronic inflammation, however research has not consistently shown this and an inverse relationship has been shown in some studies. This systematic review and meta-analysis aimed to determine the effect of probiotics and synbiotics on inflammation in individuals with prediabetes and T2D. A total of 32 randomised control trials were included in the meta-analysis and showed that certain, but not all inflammatory markers were reduced. Antioxidants were increased. The effect was especially pronounced in individuals with T2D as opposed to prediabetes. It was concluded that probiotics or synbiotics could be useful for individuals with T2D to reduce inflammation and reduce the risk for other associated diseases such as heart disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Probiotic and synbiotic supplementation may significantly reduce inflammation and oxidative stress, potentially lowering the risk of cardiovascular diseases in those with prediabetes and T2DM.
- These supplements may be particularly beneficial for individuals with T2DM and those who are overweight or obese.
- Incorporating probiotics and synbiotics into the diet could be a supportive strategy for improving metabolic health markers.
- The observed benefits vary depending on the type and duration of supplementation, suggesting that consistent, long-term use might be necessary to achieve noticeable health improvements.
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 meta-analysis and meta-regression assessed the impact of probiotics and synbiotics on inflammation, antioxidants, oxidative stress, and adipokines in prediabetes and type 2 diabetes.
Methodology
The methodology involved searching PubMed/MEDLINE, ISI Web of Science, Scopus, and Cochrane Library databases without date or language restrictions until March 2022. Study quality was evaluated.
- Inclusion criteria: Adults 18+ with prediabetes or type 2 diabetes; interventions with probiotics or synbiotics versus placebo or other treatments; and reporting on inflammatory biomarkers, adipocytokines, and oxidative stress serum biomarkers in RCTs with parallel or cross-over designs.
Results
32 RCTs with 2074 participants were analysed, mostly in Asia (26 studies) and 5 in Europe, Africa, Oceania, and America, over 4 to 24 weeks. Dosages varied, including synbiotic bread with Lactobacillus sporogenes and inulin (1×10^8 CFU, 0.07g/g, thrice daily), 300ml/day fermented milk with L. helveticus, daily synbiotic and probiotic tablets, a probiotic mixture (120g/day), synbiotics (9g, thrice daily), multistrain probiotic yoghurt (300g/day), L. sporogenes-enriched bread (40g, thrice daily), and probiotic honey (2500mg/day). Measurements included CRP (31 RCTs), TNF-α (12 RCTs), GSH (13 RCTs), MDA (12 RCTs), TAC (11 RCTs), and NO levels (8 trials).
Effects of probiotics and synbiotics:
- significantly reduced CRP levels (-0.62 mg/L, 95% CI: -0.80 to -0.44, p < 0.001, 31 RCTs), showing greater efficacy in T2DM than prediabetes, particularly in individuals with overweight.
- TNF-α levels decreased in participants with T2D or overweight (-0.48 pg/mL, 95% CI: -0.81 to -0.15, p = 0.004, 12 RCTs).
- GSH levels significantly rose (69.80, 95% CI: 33.65 to 105.95, p < 0.001, 13 RCTs), independent of trial duration or baseline BMI.
- MDA levels were significantly reduced (-0.51, 95% CI: -0.73 to -0.30, p < 0.001, 12 RCTs) in studies lasting ≥12 weeks.
- TAC significantly increased (73.59, 95% CI: 33.24 to 113.95, p < 0.001, 11 RCTs), with more pronounced effects in longer trials and with probiotics.
- NO levels improved significantly (7.49, 95% CI: 3.12 to 11.86, p = 0.001, 9 trials) in individuals with obesity.
- Positive impacts on CRP, TNF-α, MDA, and TAC were more marked in trials ≥12 weeks.
Conclusions
Probiotic or synbiotic intake may benefit those with prediabetes and T2DM, reducing CRP, TNF-α, MDA, and enhancing TAC, GSH, NO levels, especially in T2DM individuals. Effects are stronger in individuals with overweight or obesity.
Clinical practice applications:
- Probiotic and synbiotic supplementation could be recommended to reduce inflammatory biomarkers like CRP and TNF-α, especially in individuals with T2DM.
- The improvements in oxidative stress markers, such as increased TAC and GSH and decreased MDA, support the use of probiotic and synbiotic supplements in managing oxidative stress in T2DM and prediabetes.
- Longer durations (≥12 weeks) of probiotic or synbiotic supplementation may offer a more pronounced effect on antioxidant capacity.
- The findings can guide personalised nutritional recommendations, as for example improvement in inflammation biomarkers and NO were more evident in individuals with T2DM or overweight suggesting an anti-inflammatory effect primarily in these groups. Moreover, markers related to antioxidant capacity were improved in those diagnosed with prediabetes or T2DM irrespective of BMI.
Considerations for future research:
- The beneficial effects on inflammatory and antioxidant/oxidative stress markers suggest a need for larger and longer-term studies to solidify the role of probiotics and synbiotics in benefiting chronic conditions like T2DM and prediabetes.
- There is potential for investigating the specific strains of probiotics that are most effective, considering varying outcomes observed across different studies.
- Research could explore the mechanisms by which probiotics and synbiotics exert their beneficial effects, contributing to a better understanding of gut-health interactions.
- The varying responses based on BMI categories indicate a need for personalised nutrition research to optimise probiotic therapy for individual needs.
- Future studies should consider standardising the dosage and formulation of probiotics to determine the most effective therapeutic doses and combinations.
Abstract
PURPOSE Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM). METHODS We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome. RESULTS A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels. CONCLUSION A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.
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Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials.
Mitra, AK, Asala, AF, Malone, S, Mridha, MK
Diseases (Basel, Switzerland). 2023;11(4)
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Gastroenteritis is a major cause of morbidity and mortality globally and symptoms can range from mild to life-threatening. Some studies have suggested benefits of probiotics in the treatment of gastroenteritis in children whilst in adults, results are inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics on acute and chronic gastroenteritis in adults. 35 clinical trials were included in the systematic review and 22 in the meta-analysis. Of these, 23 dealt with inflammatory bowel disease, 5 with pouchitis, 3 with antibiotic-induced diarrhoea, 2 with Helicobacter pylori infection and one each with diverticulitis and acute watery diarrhoea. 27 (77%) of studies showed some benefits of probiotic administration. The meta-analysis of 22 studies did not show a statistically significant benefit of probiotics. Although statistical analysis showed the studies to be homogenous, the authors point out that studies differed widely in aetiologies and probiotics used. A subgroup analysis of 8 studies in patients with ulcerative colitis also showed no benefit. In all studies, probiotics were well tolerated and no adverse side effects were reported. The authors concluded that further research is needed to help identify the most appropriate use of probiotics for the different types of gastroenteritis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For chronic inflammatory gastroenteritis conditions in adults, probiotics were effective in treating and preventing relapse
- In ulcerative colitis, probiotics were not effective and adverse events outweighed the benefits
- No safety concerns were found for probiotic use in any studies
- Aetiologies, disease severity and duration as well as the type of probiotics used were widely diverse.
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
To date, evidence has been mixed for probiotic effectiveness in gastrointestinal syndromes associated with gastroenteritis. The aim of this study was to review current evidence on the effect of probiotics on gastroenteritis in adults.
Methods
This was a systematic review (n=35; total sample size 4577, median 44) and meta-analysis (n=22) of randomised controlled trials. Quality was assessed using CADIMA as per a rating scale (0 to 4) and standards of critical appraisal.
Results
All 35 studies on gastroenteritis included participants with chronic diarrhoea of diverse aetiologies such as IBD, antibiotic-associated, except one which had acute watery diarrhoea.
51% (n=18) of studies assessed the effects of probiotics in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). 60% (n=21) used multiple strains of probiotics while the rest used single strains. Lactobacilli, Bifidobacteria, Escherichia and Streptococcus were the most common and only a few studies administered probiotics with another conventional treatment.
19 studies (55%) rated highly in terms of quality while 15 (43%) scored moderately. The majority (63%) of the 27 studies where probiotics were shown to be effective were of high quality.
Systematic review results:
- 27/53 studies (77%) showed a favourable response after using probiotics (resolution, improvement, remission or no relapse), mostly in patients with IBDs
- 7 studies (20%) found probiotics to be ineffective
- 1 study was inconclusive
- Multiple strain probiotics (VSL #3) was found to be most effective in IBD
- All administered probiotics were well tolerated with no adverse side effects although caution in immunocompromised patients was mentioned in several studies.
The meta-analysis results:
- Overall effectiveness for 22 studies (p=0.37) highlighted there was not enough evidence that the intervention was more protective than controls.
- Probiotics were not effective in UC (p = 0.28), and adverse events caused by probiotics may outweigh the benefits in studies with UC patients.
Conclusion
While benefits of effectiveness were found for probiotic use in gastroenteritis in adults, results from the systematic review and meta-analysis showed a mixed effect.
Clinical practice applications:
- Based on the systematic review, probiotics may be an effective treatment or adjuvant treatment for gastroenteritis but ineffective for around 20% of patients
- It is worth noting that combined therapy with standard treatment showed effective results
- Beneficial effects of probiotics in other key clinical outcomes including disease prevention, relapse, quality of life, morbidity were found
- While the results are interesting it is difficult to apply them in practice as the type of probiotics used were widely different as were the causes, severity and duration of gastroenteritis.
Considerations for future research:
- Further and larger studies would be beneficial to understand the benefits of probiotics in terms of single therapy or in combination with standard treatment particularly for UC, CDs, gastroenteritis not due to viral infection
- Individual-level data instead of aggregated data could give a better idea of effectiveness of probiotics in the future
- In this study aetiologies and the type, dosage, duration of probiotics used were widely diverse therefore systematic reviews and meta-analysis on specific conditions, specific probiotic strains and combinations would be beneficial.
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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5.
The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
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 paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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6.
A Low-FODMAP Diet Provides Benefits for Functional Gastrointestinal Symptoms but Not for Improving Stool Consistency and Mucosal Inflammation in IBD: A Systematic Review and Meta-Analysis.
Peng, Z, Yi, J, Liu, X
Nutrients. 2022;14(10)
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Plain language summary
The low-FODMAP diet eliminates carbohydrates that cannot be easily digested in order to reduce functional gastrointestinal symptoms associated with irritable bowel disease (IBD). The symptoms of irritable bowel disease include abdominal pain and bloating. This systematic review and meta-analysis aimed to evaluate whether a low-FODMAP diet can alleviate functional gastrointestinal symptoms in individuals with inflammatory bowel disease. In comparison with a regular diet, a low-FODMAP diet significantly reduced symptoms of bloating, wind, flatulence, abdominal pain, fatigue, and lethargy in patients with IBD. In addition, patients with Crohn's disease have achieved remission or reduced symptoms after following a low-FODMAP diet. Healthcare professionals can use this study to understand better the effects of a low-FODMAP diet on patients with IBD who have functional gastrointestinal symptoms. Further robust studies are, however, required to evaluate the evidence's robustness and identify the mechanism behind the improvement of symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- LFD use in IBD improved symptoms of bloating, wind or flatulence, borborygmi, abdominal pain, and fatigue or lethargy, but not nausea and vomiting.
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 meta-analysis assesses the efficacy of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (LFD) in inflammatory bowel disease [IBD: ulcerative colitis (UC) and Crohn’s disease (UC)] participants with functional gastrointestinal symptoms (FGSs).
Methods
A search was performed on PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), WanFang (Chinese) Database up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies (4 randomised controlled trials, 5 non-randomised studies) with a total of 351 participants diagnosed with IBD were included, and compared LFD with a placebo diet or normal diet (ND), overall and individual
LFD Effects of FGS:
- Overall 9 studies: an improvement (0.47, 0.33–0.66, p = 0.0000)
- No difference in the subgroup classified by disease type
- CD and UC: no improvement
Individual improvement:
- Bloating (0.37, 0,24-0,57, p=0.0000); wind or flatulence (0.38, 0,28-0,51, p=0.0000); borborygmi (0.48, 0,26-0,89, p=0.0000), abdominal pain (0.5, 0,37-0,68, p=0.0000), fatigue/lethargy (0.71, 0,61-0,82, p=0.0000)
- No difference in nausea and vomiting (0.54, 0,22-1,32, p=018)
IBS Quality of Life Score:
- 2 studies: reduced Short IBD Questionnaire (SIBDQ) score (11.24, 6.61-15.87, p=0.0000)
Bristol Stool Form Chart:
- 2 studies: normal stool consistency (type 3-4); no difference (5.99, 0.17-216.51, p=0.33)
- 2 other studies: no difference (-0.17, 0.48 - 0.15, p=0.30)
Diseases activity (Harvey-Bradshaw index):
- 2 studies using the Mayo score: no difference (-32, -1,09-0.45, p=0.41)
- 3 studies using BHi score: reduction (-1.09, -1,77-0.42, p=0.002)
Faecal calprotectin:
- 2 studies: no change (-16.03, -36,78-4.73, p=0.13)
Limitations
- Comparison diets were not standardised, suggesting the potential of different dietary habits to bias results..
- Heterogeneity of included studies, and the relatively small sample size of the studies can reduce the reliability of the results.
Conclusion
While the study found inconsistent definition standards for FGS, all the nine studies showed that LFD was associated with an improvement in some symptoms.
Clinical practice applications:
- This study suggests that IBD patients with FGSs may benefit from LFD treatment with the assistance of a healthcare professional.
Considerations for future research:
- This study has shown that LFD can improve FGSs in IBD, but further research with a larger sample size and more comprehensive analysis is warranted to replicate the results.
- The description of the findings and Quality of Life data are a little unclear. The impact on Quality of Life warrants further investigation, as clinicians need to consider the impact of following a restrictive diet on Quality of Life.
Abstract
BACKGROUND A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (LFD) is claimed to improve functional gastrointestinal symptoms (FGSs). However, the role of LFD in inflammatory bowel disease (IBD) patients with FGSs remains unclear. OBJECTIVE To systematically assess the efficacy of LFD in IBD patients with FGSs. METHODS Six databases were searched from inception to 1 January 2022. Data were synthesized as the relative risk of symptoms improvement and normal stool consistency, mean difference of Bristol Stool Form Scale (BSFS), Short IBD Questionnaire (SIBDQ), IBS Quality of Life (IBS-QoL), Harvey-Bradshaw index (HBi), Mayo score, and fecal calprotectin (FC). Risk of bias was assessed based on study types. A funnel plot and Egger's test were used to analyze publication bias. RESULTS This review screened and included nine eligible studies, including four randomized controlled trials (RCTs) and five before-after studies, involving a total of 446 participants (351 patients with LFD vs. 95 controls). LFD alleviated overall FGSs (RR: 0.47, 95% CI: 0.33-0.66, p = 0.0000) and obtained higher SIBDQ scores (MD = 11.24, 95% CI 6.61 to 15.87, p = 0.0000) and lower HBi score of Crohn's disease (MD = -1.09, 95% CI -1.77 to -0.42, p = 0.002). However, there were no statistically significant differences in normal stool consistency, BSFS, IBS-QoL, Mayo score of ulcerative colitis, and FC. No publication bias was found. CONCLUSIONS LFD provides a benefit in FGSs and QoL but not for improving stool consistency and mucosal inflammation in IBD patients. Further well-designed RCTs are needed to develop the optimal LFD strategy for IBD.
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7.
Impact of Probiotics on the Performance of Endurance Athletes: A Systematic Review.
Díaz-Jiménez, J, Sánchez-Sánchez, E, Ordoñez, FJ, Rosety, I, Díaz, AJ, Rosety-Rodriguez, M, Rosety, MÁ, Brenes, F
International journal of environmental research and public health. 2021;18(21)
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Plain language summary
The relationship between the gut microbiome and exercise has recently been explored to ascertain potential methods of improving athletic performance. Athletes have begun utilising probiotics to improve performance, support the immune system and reduce gastrointestinal problems, however no systematic review has been done to assess the efficacy behind these notions. The aim of this study is to review the use of probiotics in endurance athletes and assess both the direct and indirect associative factors. This review included nine studies and found improvements in athletic performance, oxidative stress markers, immune support, and incidence of upper respiratory tract infections with probiotic use. While there is little scientific evidence on the causative relationship between probiotics and performance, the authors conclude probiotics can enhance athletic performance by ameliorating the indirect consequences of oxidative stress and infection.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Endurance athletes may take probiotic supplements to support immune or GI health or for other reasons
- Currently there is little evidence that probiotics directly or specifically enhance athletic performance
- Probiotic supplementation potentially impacts on immune health particularly during intensive training and may facilitate muscle recovery or maintain performance
- Whilst probiotics may reduced GI symptom frequency and severity, further research is clearly warranted
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:
- There is current interest in the potential therapeutic benefits of probiotic strategies to support training and in-race performance for endurance athletes.
- Probiotic supplements are typically used by endurance athletes to limit or prevent upper respiratory tract infections (URTIs), reduce oxidative stress, support the immune system and modulate gastrointestinal function.
- Based on a limited number of articles sourced in this review (n=26), only 9 met the underlying quality and inclusion criteria. This highlights an important need for further research to be undertaken in this area.
- The review highlighted that different preparations, number of bacterial colony-forming units (CFUs), species type, timecourse and study objectives makes it difficult to determine fundamental conclusions on the efficacy of probiotics.
- That said, papers reviewed indicated the potential for a 55% increase in anti-inflammatory cytokines, reduced prevalence of URTIs, reduced Epstein-Barr and cytomegalovirus citrate antibodies, and improved recovery times.
- Probiotic supplementation likely enhances microbiota diversity and may indirectly support increased training load, and performance maintenance through immune defence. However, there were no indications that endurance performance was specifically enhanced.
Clinical practice applications:
- Most of the papers reviewed used formulae containing either Lactobacillus spp. (e.g. Plantarum, Acidophilus, Casei Shirota) or Bifidobacterium spp. (e.g. animalis subsp., bifidum, lactis, longum subsp.) or combinations. There was little mention of prebiotic or symbiotic strategies.
- Any impact of probiotics on exercise performance is likely to relate to both immune modulation and/or mechanisms leading to reduced muscle damage.
- Surprisingly, there was only partial mention of the use of probiotics for GI support and several notable papers were not included in the review. That said, the authors did note that with increased prevalence of exercise-induced gastrointestinal symptoms with endurance sport due to acute GI hypoperfusion and localised ischemia, acute probiotic strategies have resulted in reduced GI symptom frequency and severity in athletes.
- Importantly no adverse events following probiotic supplementation in endurance athletes were reported.
Considerations for future research:
- Clearly further research is warranted in terms of probiotic strain specific benefits both in training and in-race event effectiveness.
- The authors reported that there were no studies found on the effect of probiotics on hormonal or nervous systems in endurance athletes.
- Further research is needed to consider the impact of acute versus chronic probiotic use on intestinal metabolites, especially considering recent interactions between specific bacterial strains and short-chain fatty acid production being associated with performance (see: https://www.nutrition-evidence.com/article/31235964?term=31235964.
Abstract
BACKGROUND Probiotic supplements contain different strains of living microorganisms that promote the health of the host. These dietary supplements are increasingly being used by athletes to improve different aspects such as athletic performance, upper respiratory tract infections (URTIs), the immune system, oxidative stress, gastrointestinal (GI) problems, etc. This study aimed to identify the current evidence on the management of probiotics in endurance athletes and their relationship with sports performance. METHODS A systematic review of the last five years was carried out in PubMed, Scopus, Web of science, Sportdiscus and Embase databases. RESULTS Nine articles met the quality criteria. Of these, three reported direct benefits on sports performance. The remaining six articles found improvements in the reduction of oxidative stress, increased immune response and decreased incidence of URTIs. There is little scientific evidence on the direct relationship between the administration of probiotics in endurance athletes and sports performance. CONCLUSIONS Benefits were found that probiotics could indirectly influence sports performance by improving other parameters such as the immune system, response to URTIs and decreased oxidative stress, as well as the monitoring of scheduled workouts.