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Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.
Ni Lochlainn, M, Bowyer, RCE, Moll, JM, García, MP, Wadge, S, Baleanu, AF, Nessa, A, Sheedy, A, Akdag, G, Hart, D, et al
Nature communications. 2024;15(1):1859
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Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.
Abstract
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
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Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis.
Zhang, Q, Chen, B, Zhang, J, Dong, J, Ma, J, Zhang, Y, Jin, K, Lu, J
BMC psychiatry. 2023;23(1):477
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Major depressive disorder (MDD) is a mood disorder that impairs psychosocial function and quality of life. Recent studies show that prebiotics, probiotics, and synbiotics reveal a novel way to treat psychiatric disorders such as depression through the microbiota-gut-brain axis. The aim of this study was to evaluate the effectiveness of prebiotics, probiotics and synbiotics in alleviating depressive symptoms. This study was a meta-analysis of thirteen studies with a total of 786 participants who were allocated to the intervention group (n=427) and the placebo group (n=359). Results showed that the overall effects of probiotics, prebiotics and synbiotics on depressive symptoms were significantly superior to those of placebo. Additionally, biological sex was a vital factor that influenced patients’ responses to the treatment. Authors concluded that agents that manipulate gut microbiota might become a novel approach to treat patients with mild-to-moderate depression.
Abstract
Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.
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Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review.
Avelar-Rodríguez, D, Peña-Vélez, R, Popov, J, Hill, L, Ryan, PM
Revista espanola de enfermedades digestivas. 2023;115(8):418-427
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Non-alcoholic fatty liver disease (NAFLD), as a direct result of the escalating childhood obesity epidemic, is a significant public health issue globally. NAFLD is the most common cause of chronic liver disease in the paediatric population. The aim of this study was to assess the quality of evidence currently available for the use of microbial therapies (i.e., prebiotics, probiotics, and synbiotics) in the treatment of NAFLD in children with obesity. This study was a systematic review and meta-analysis of five randomised controlled studies. Results showed that although there is a range of promising effects on both clinical and biochemical parameters, significant interstudy discrepancies reduce reliability and generalisability of these results. Authors concluded there is insufficient evidence to support the beneficial role of probiotics and synbiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials.
Abstract
BACKGROUND non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.
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Effectiveness of Probiotic, Prebiotic, and Synbiotic Supplementation to Improve Perinatal Mental Health in Mothers: A Systematic Review and Meta-Analysis.
Desai, V, Kozyrskyj, AL, Lau, S, Sanni, O, Dennett, L, Walter, J, Ospina, MB
Frontiers in psychiatry. 2021;12:622181
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Maternal mental health problems in the perinatal period are a global public health challenge. As many as one in five women develop depression and/or anxiety in the postpartum period, making them the most common complications of pregnancy and delivery. The aim of this study was to evaluate the evidence on the administration of prebiotic, probiotic, and/or synbiotic supplements during pregnancy to reduce the risk of mental health problems in the perinatal period. This study is a systemic review and meta-analysis of four studies of which three where included in the qualitative and quantitative synthesis. Results indicate limited evidence about the effectiveness of probiotics administered during pregnancy to reduce the risk of maternal mental health disorders and highlighted the lack of evidence on prebiotics and synbiotics supplementation to inform their use for similar purposes. Authors conclude that there is the need for future trials targeting microbiota interventions that test probiotic/prebiotic/synbiotic interventions that redress specific dysbioses in pregnancy gut microbiota that arise from poor mental health.
Abstract
Introduction: There is an emerging interest in modulating the gut microbiota to target the gut-brain axis and improve maternal mental health in the perinatal period. This systematic review evaluated the effectiveness of prebiotics, probiotics, and synbiotics supplementation during pregnancy to reduce the risk of maternal mental health problems in the perinatal period. Methods: Electronic biomedical databases and clinical trial registries were searched from database inception through August 2020 to identify randomized controlled clinical trials (RCTs) evaluating the effect of probiotic, prebiotic, or synbiotic supplements administered to women during pregnancy on measures of perinatal depression, anxiety, and other mental health outcomes. Study selection, risk of bias appraisal, and data extraction were independently performed by two reviewers. Pooled mean differences (MD) and odds ratios (pOR) with 95% confidence intervals (CI) were calculated in random-effects meta-analyses for the outcomes of interest in the review. Results: From 3,868 studies identified through the search strategy, three RCTs of low risk of bias involving 713 participants were included, all three testing probiotics. There were no differences between probiotics and control groups in the mean depression scores (MD -0.46; 95% CI -2.16, 1.25) at end of follow-up. Although statistical significance was not achieved, probiotics showed an advantage in the proportion of participants scoring below an established cut-off for depression (pOR 0.68; 95% CI 0.43, 1.07). Compared to placebo, probiotics in pregnancy reduced anxiety symptoms (MD -0.99; 95% CI -1.80, -0.18); however, this advantage was not translated in a reduction in the proportion of participants scoring above an established cut-off for anxiety (pOR 0.65; 95% CI 0.23, 1.85). There were no differences between probiotics and control groups in global mental health scores at end of follow-up (MD 1.09; 95% CI -2.04, 4.22). Conclusion: There is limited but promising evidence about the effectiveness of probiotics during pregnancy to reduce anxiety symptoms and reduce the proportion of women scoring ABOVE a cut-off depression score. There is a lack of RCT evidence supporting prebiotics and synbiotics supplementation for similar purposes in the perinatal period. More research is needed before prebiotics, probiotics, and synbiotics are recommended to support maternal mental health and well-being in the perinatal period. Systematic Review Registration: PROSPERO, CRD42019137158.
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Role of gut microbiota in cardiovascular diseases.
Novakovic, M, Rout, A, Kingsley, T, Kirchoff, R, Singh, A, Verma, V, Kant, R, Chaudhary, R
World journal of cardiology. 2020;12(4):110-122
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Cardiovascular disease (CVD) is the leading cause of death globally. CVD risk factors such as aging, obesity, dietary patterns and a sedentary lifestyle induce changes in the gut microbiota. The resulting dysbiosis is associated with intestinal inflammation leading to reduced integrity of the gut barrier. When this happens, certain components enter the circulation which may facilitate the development of CVD. Looking at the gut microbiota as a locus of intervention is therefore a novel and relevant avenue for future research. This article reviews the normal function and composition of the gut microbiome, the mechanisms leading to reduced gut barrier integrity (leaky gut syndrome), its link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. The alteration of the gut microbiome is a potential therapeutic target in managing CVD. However, further experiments are needed to see if the effects observed in animal studies can be translated to humans.
Abstract
The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.
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Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.
Gasmi, A, Noor, S, Tippairote, T, Dadar, M, Menzel, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;215:108409
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With the continuing spread of COVID-19 and lack of any approved treatments, this paper examines possible strategies for prevention. The data emerging so far highlights that individual health status plays a critical role in determining clinical severity of COVID-19 symptoms ranging from asymptomatic, mild, moderate, to death. Metabolic status, as determined by a patient’s diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors can therefore be considered preventative strategies to improve the severity of COVID-19 outcomes. Social distancing and personal hygiene are stated as the most effective strategies to prevent or slow spread of the disease. However individual health status, age and the presence of pre-existing comorbidities influences outcomes, as shown by global data highlighting a prevalence in older, males with metabolic conditions; hypertension in 23.7% patients and diabetes in 16.2% of patients. Older males appear more prone to infectious diseases with high pro-inflammatory immune responses and low adaptive immune responses than an older woman. Diet and healthy intestinal and respiratory tract microbiota may also influence immune system competence. Numerous micronutrients are essential for immunocompetence, particularly vitamin A, C, D, E, Bs, iron, selenium, and zinc. A balanced diet, high in colourful fruits and vegetables with a variation of prebiotic fibres, probiotics, and plant polyphenols and phytonutrients, help promote a healthy, diverse microbiota. Oral probiotics may also be beneficial to vulnerable individuals. Vitamin D supplementation is also proving helpful in prevention of acute respiratory tract infections. Other lifestyle factors such as smoking and exposure to environmental toxins should also be considered. Together these preventative measures may reduce personal risk of getting the disease.
Abstract
It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.
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The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases.
Xu, H, Liu, M, Cao, J, Li, X, Fan, D, Xia, Y, Lu, X, Li, J, Ju, D, Zhao, H
Journal of immunology research. 2019;2019:7546047
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The human gut, or intestines, are populated with commensal bacteria which live in harmony with us and support various biological functions. The main role of the gut microbiota is to maintain the homeostasis of our immune system. It does this by maintaining the integrity of the intestinal lining and helping with digestive processes, production, and absorption of nutrients, and harvesting of immune cells. Our gut microbiome develops throughout infancy and confers benefits in adulthood and so any disruption to its development may impact on health. An imbalance between these helpful bacteria and more harmful pathogenic bacteria, which are also present in smaller amounts, is called dysbiosis and is a common factor in many autoimmune conditions. Autoimmune conditions are characterised by an over-active immune system where immune cells attack our own body. Imbalances in gut microbiota are also common, and diet is thought to be a key factor alongside other genetic and environmental factors. Evidence suggests that long-term dysbiosis may trigger autoimmune disease, amplify disease progression or both, as seen in studies on Arthritis, Lupus, Inflammatory bowel disease. The gut microbiota can be partially restored and supported with antimicrobial interventions, prebiotics, and selective probiotics. The review concludes that therapies targeting the gut microbiota may be effective in the future prevention or treatment of autoimmune diseases.
Abstract
The human gut-resident commensal microbiota is a unique ecosystem associated with various bodily functions, especially immunity. Gut microbiota dysbiosis plays a crucial role in autoimmune disease pathogenesis as well as in bowel-related diseases. However, the role of the gut microbiota, which causes or influences systemic immunity in autoimmune diseases, remains elusive. Aryl hydrocarbon receptor, a ligand-activated transcription factor, is a master moderator of host-microbiota interactions because it shapes the immune system and impacts host metabolism. In addition, treatment optimization while minimizing potential adverse effects in autoimmune diseases remains essential, and modulation of the gut microbiota constitutes a potential clinical therapy. Here, we present evidence linking gut microbiota dysbiosis with autoimmune mechanisms involved in disease development to identify future effective approaches based on the gut microbiota for preventing autoimmune diseases.
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The Efficacy of Probiotics, Prebiotic Inulin-Type Fructans, and Synbiotics in Human Ulcerative Colitis: A Systematic Review and Meta-Analysis.
Astó, E, Méndez, I, Audivert, S, Farran-Codina, A, Espadaler, J
Nutrients. 2019;11(2)
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It is thought that ulcerative colitis (UC) may be caused by an excessive immune response to endogenous bacteria in genetically predisposed individuals, and therefore that manipulating of the gut flora may be of benefit. Microbial diversity and intestinal microbiota stability are lower in patients with inflammatory bowel disease (including UC), than in healthy people. This systematic review and metanalysis looked at clinical trials using probiotics, prebiotics and synbiotics (a combination of pro- and prebiotics) in UC. 18 papers were included, with a total of 1491 adult and 69 children. 16 of these were on probiotics, one on prebiotics and one on synbiotics. Outcomes considered in this systematic review were the effects on short chain fatty acids (SCFAs, metabolic end products of gut bacteria which have a beneficial effect on immune and gut health), inflammation levels, composition of faecal microbiota and UC remission. In trials on inactive UC patients, the faecal concentration of SCFAs did not differ significantly between the probiotic and placebo groups, whilst in trials with active UC patients, SCFAs significantly increased after probiotic supplementation. All studies reported a significant reduction in inflammation. Meta-analysis of studies which looked at induction/maintenance of remission by probiotics showed that this depends on a) the type of disease activity score used to assess remission, and b) the type of probiotics used, with bifidobacteria containing probiotics, VSL3 and Mutaflor showing benefits, but studies without bifidobacteria being no different from placebo. The authors conclude that bifidobacteria containing probiotics seem to be beneficial in terms of reaching remission in patients with UC, although there is insufficient information on necessary dose and duration of treatment. They note that there are only few studies on prebiotics and synbiotics and are calling for a standardisation of scales to assess remission.
Abstract
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13⁻2.15, p-value = 0.007, I² = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23⁻2.43, p-value = 0.002, I² = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
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Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis.
Liang, S, Wu, X, Hu, X, Wang, T, Jin, F
International journal of molecular sciences. 2018;19(6)
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Emerging research indicates that major depression is not just a mental disorder but also a systemic disease. In depression, the brain-gut axis, the bidirectional pathway that connects the brain and gut, is thought to be disturbed. This disruption is hypothesised to be a major pathological basis of depression. The aim of this paper is to explore this hypothesis by reviewing the current literature. According to the current literature, the authors found research stating the gut microbiota of depressed patients is significantly different from that of healthy controls. Additionally, disturbances or abnormalities in the gut can influence the susceptibility of onset of depression, while restoration of the gut will alleviate depression. Based on these findings, the authors conclude depression is closely related with the condition of the brain-gut axis, and that restoring the normal condition of gut microbiota may aid in the therapy of depression. The authors expect therapies that target gut microbiota will play an important role in the treatment and prevention of depression in the future.
Abstract
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain⁻gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota⁻gut⁻brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.
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Psoriasis and Microbiota: A Systematic Review.
Benhadou, F, Mintoff, D, Schnebert, B, Thio, HB
Diseases (Basel, Switzerland). 2018;6(2)
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Psoriasis is an autoimmune inflammatory skin disease that causes red, itchy, flaky and scaly skin. Skin integrity and function are critically dependent on the microbial population on it. Based on this systematic review, the immune system's interaction with microbes on the skin was examined and its relationship to psoriasis. T-cell mediated inflammation is characteristic of psoriasis where interaction between type IV collagen and α1β1 integrin, a collagen receptor, occurs. In psoriatic skin lesions, Firmicutes were predominant, while Actinobacteria were less prevalent. Psoriasis exacerbations are also associated with an exacerbated number of fungi, Malassezia species, in skin lesions. As therapeutic strategies for psoriasis, this systematic review suggests adhering to a gluten-free diet and incorporating prebiotics and probiotics such as Lactobacillus. However, further research is needed to develop specific therapeutic and skin modulation strategies. Health care professionals can benefit from this systematic review by understanding the pathophysiology behind psoriasis and possible therapeutic strategies to consider.
Abstract
BACKGROUND Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. AIM: Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. CONCLUSIONS Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects.