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An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: a single arm open label trial.
Rodenes-Gavidia, A, Lamelas, A, Bloor, S, Hobson, A, Treadway, S, Haworth, J, Vijayakumar, V, Naghibi, M, Day, R, Chenoll, E
Frontiers in cellular and infection microbiology. 2023;13:1240267
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The human gut microbiota is a key mediator of host health and is known to affect many physiological processes, such as digestion, metabolism, immune function and inhibition of pathogen colonisation. The gut microbiome can be impacted by many extrinsic factors. The aim of this study was to assess both compositional and functional changes in the microbiome of healthy individuals using shotgun metagenomics following 8-weeks of daily multi-strain probiotic intake. This study was a single-arm open-label study which enrolled a total of 41 healthy adult males and females between 18 to 40 years old. Results showed that alpha- and beta-diversity of the faecal microbiota structure was not significantly altered in response to probiotic intake. However, significant changes were observed when functional genes were assessed. Abundance of certain genes involved in several functional pathways were also significantly altered. Additionally, there were no significant changes in stool frequency or consistency, faecal biochemistry, or breath tests of methane and hydrogen observed. Authors conclude that the findings of their study have the potential to provide insights into the underlying mechanisms of action of the 14-strain probiotic blend in healthy adults.
Abstract
BACKGROUND Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations. PURPOSE The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic. METHODS We analysed the effect of a 14-strain probiotic blend (Bacillus subtilis NCIMB 30223, Bifidobacterium bifidum NCIMB 30179, B. breve NCIMB 30180, B. infantis NCIMB 30181, B. longum NCIMB 30182, Lactobacillus helveticus NCIMB 30184, L. delbrueckii subsp. bulgaricus NCIMB 30186, Lacticaseibacillus paracasei NCIMB 30185, Lactiplantibacillus plantarum NCIMB 30187, Lacticaseibacillus rhamnosus NCIMB 30188, L. helveticus NCIMB 30224, Lactobacillus salivarius NCIMB 30225, Lactococcus lactis subsp. lactis NCIMB 30222, and Streptococcus thermophilus NCIMB 30189), on the faecal microbiota of healthy young adults (n=41) in a single arm study. The adults consumed 4 capsules daily of the 14 strain blend(8 billion colony forming units/day) for 8 weeks. Compositional and functional changes in faecal microbiota before and after supplementation were assessed using shotgun metagenomic sequencing. Fasting breath analysis, faecal biochemistry and bowel habits were also assessed. RESULTS In healthy adult participants, no significant changes to the overall alpha- or beta-diversity was observed after 8 weeks of multi-strain probiotic supplementation. However, in a simplified model that considered only time and individual differences, significant decreases (p < 0.05) in family Odoribacteraceae and Bacteroidaceae abundance and a significant increase (p < 0.05) in genus Megamonas abundance were observed. At a functional level, there were significant changes in functional gene abundance related to several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly. No significant changes in stool form or frequency, fecal biochemistry, or methane and hydrogen breath tests were observed. CONCLUSION In healthy young adults, overall alpha- and beta-diversity did not change in response to probiotic intake even though modest compositional changes at the family and genus level were observed. However, at functional level, results identified changes in gene abundance for several functional pathways.
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The Effect of Kefir Supplementation on Improving Human Endurance Exercise Performance and Antifatigue.
Lee, MC, Jhang, WL, Lee, CC, Kan, NW, Hsu, YJ, Ho, CS, Chang, CH, Cheng, YC, Lin, JS, Huang, CC
Metabolites. 2021;11(3)
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Compared to sedentary people, athletes exhibit a much more abundant and diverse composition of gut bacteria. Hence the relationship between gut microbes and energy usage and exercise performance has attracted much attention in recent years. Probiotics and prebiotic-related products have demonstrated the potential to enhance metabolic pathways and influence energy levels, energy consumption and exercise performance. And previous studies demonstrated positive effects on exercise endurance associated with the consumption of kefir, a fermented dairy product containing Lactobacilli species as part of the microbial symbiosis. This study investigated whether kefir can promote changes in the gut microbiota, improve exercise endurance performance, and influences fatigue during and after exercise. The study enrolled sixteen, untrained 20–30-year-old for a double-blind crossover design study, supplementing with SYNKEFIR™ for 28 days whilst observing changes in metabolic markers, body composition, exercise endurance and faecal gut bacteria. In summary, supplementation with SYNKEFIR™ significantly improved exercise performance and reduced the production of lactic acid after exercise. In addition, kefir supplementation seemed to reduce fatigue and accelerated the recovery from fatigue after exercise, with a marked reduction in lactic acid production after exercise. Though kefir supplementation had no significant effect on other post-exercise fatigue biochemical indicators nor did it induce notable changes in gut bacteria composition. As SYNKEFIR™ is a starter culture isolated from traditional kefir it could be expected that other traditional kefir products would have similar effects. Kefir as a food product is suited to a wide range of people, and it could be considered part of a healthy diet plan for untrained individuals wishing to support their exercise performance.
Abstract
Kefir is an acidic, carbonated, and fermented dairy product produced by fermenting milk with kefir grains. The Lactobacillus species constitutes an important part of kefir grains. In a previous animal study, kefir effectively improved exercise performance and had anti-fatigue effects. The purpose of this research was to explore the benefits of applying kefir to improve exercise performance, reduce fatigue, and improve physiological adaptability in humans. The test used a double-blind crossover design and supplementation for 28 days. Sixteen 20-30 year-old subjects were divided into two groups in a balanced order according to each individual's initial maximal oxygen uptake and were assigned to receive a placebo (equal flavor, equal calories, 20 g/day) or SYNKEFIR™ (20 g/day) every morning. After the intervention, there were 28 days of wash-out, during which time the subjects did not receive further interventions. After supplementation with SYNKEFIR™, the exercise time to exhaustion was significantly greater than that before ingestion (p = 0.0001) and higher than that in the Placebo group by 1.29-fold (p = 0.0004). In addition, compared with the Placebo group, the SYNKEFIR™ administration group had significantly lower lactate levels in the exercise and recovery (p < 0.05). However, no significant difference was observed in the changes in the gut microbiota. Although no significant changes in body composition were found, SYNKEFIR™ did not cause adverse reactions or harm to the participants' bodies. In summary, 28 days of supplementation with SYNKEFIR™ significantly improved exercise performance, reduced the production of lactic acid after exercise, and accelerated recovery while also not causing any adverse reactions.
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Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease.
Dimidi, E, Cox, SR, Rossi, M, Whelan, K
Nutrients. 2019;11(8)
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Fermented foods have grown in popularity due to their proposed health benefits but there is limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health. This review paper looks at non-dairy fermented foods which have been studied in at least one RCT: kefir, sauerkraut, natto, and sourdough bread. The health benefits are attributed to the high ratio of probiotic microorganisms, metabolites, or ability to convert compounds into active metabolites, as well as prebiotics and vitamins contained in these foods. Kimchi has the greatest evidence from epidemiological and case control studies investigating risk of gastric cancers. Different food composition of kimchi is shown to both increase and decrease risks, whilst it had no impact on H. pylori levels. There were no studies on kefir in functional bowel disorders however, it was shown to help lactose malabsorption and reduce H. pylori levels. A small RCT on Sauerkraut showed it reduced IBS severity in patients and increased in vitro activity of key liver and kidney detoxifying enzymes. There are small pockets of data that show that tempeh may influence gut microbiota in humans, and that natto may increase bifidobacterial and short-chain fatty acids in healthy volunteers. There are numerous limited cohort studies on miso and cancer risk but no studies on gastrointestinal conditions. Finally, sourdough was shown to reduce FODMAPS and be better tolerated in IBS patients, reducing bloating, nausea and discomfort. Overall, all the studies provide insufficient evidence on fermented foods and gastrointestinal health.
Abstract
Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.
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Small Intestinal Bacterial Overgrowth in Children: A State-Of-The-Art Review.
Avelar Rodriguez, D, Ryan, PM, Toro Monjaraz, EM, Ramirez Mayans, JA, Quigley, EM
Frontiers in pediatrics. 2019;7:363
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Small intestinal bacterial overgrowth (SIBO) occurs when microorganisms overpopulate the small intestine and is characterised by gastrointestinal symptoms such as abdominal pain, diarrhoea, and flatulence. This review focuses on paediatric SIBO, known to be increasing, with emphasis on the impact on gut microbiota. The gut microbiota is influenced by several factors including genetics, vaginal delivery, exercise and diet. SIBO in children has been studied in the context of stunting, irritable bowel syndrome (IBS), obesity, and related to use of proton pump inhibitors (PPIs). This review analysed 149 studies published since 2000 through till May 2019 with the aim of presenting the most up-to-date information. Risk factors included gastric acids and medications which suppress this activity, intestinal motility disturbances leading to bacterial overgrowth, anatomical anomalies where there is an absence of one or more intestinal valves, and poor socioeconomic status and diet. The review concluded that the recommended diagnosis is by methane and hydrogen breath testing and that Gold Standard treatment is antibiotic ‘rifaximin’ at 1,200 mg/d, reduced to 600 mg/d for 1 week in children. Alternative treatments discussed include FODMAP diets and probiotic protocols with best results coming from combining antibiotic and probiotic protocols. It concludes that SIBO in children is heterogenous and poorly understood and that a better diagnostic criteria is necessary in paediatrics.
Abstract
Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.
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Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study.
Vitellio, P, Celano, G, Bonfrate, L, Gobbetti, M, Portincasa, P, De Angelis, M
Nutrients. 2019;11(4)
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Functional gastrointestinal diseases (FGIDs) are the most common cause of gastrointestinal disturbance in global population. Probiotic supplementation is a valid approach to maintain the balance of the intestinal microbiota [micro-organisms], the composition of which could be altered by several factors. The aim of this study is to investigate the effects of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 [probiotics] with vitamin B6 (ZR) on symptoms, gut microbiota, and metabolome in a cohort of patients with persisting FGIDs on a lactose-free diet. The study is a cross-over randomised double-blind placebo-controlled study which enrolled 23 subjects. Subjects were randomly assigned to one of the two groups: ZR or placebo. Results indicate consistent amelioration of some gastrointestinal symptoms, intestinal microbiota, and related metabolism with ZR, compared with placebo. Moreover, faecal microbiome differed between the ZR and placebo group, and ZR drove the enrichment of several genera involved in lactose [sugar naturally found in milk] digestion including Bifidobacerium. Authors conclude that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in subjects with lactose intolerance and persistent FGIDs through a positive modulation of gut microbial composition and relative metabolism.
Abstract
Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.
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Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.
Rao, SSC, Rehman, A, Yu, S, Andino, NM
Clinical and translational gastroenterology. 2018;9(6):162
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D-lactic acid is produced by intestinal bacteria and a rise in levels can lead to D-lactic acidosis, causing neurological changes such as slurred speech and gait disturbances. This is frequently observed in short bowel syndrome. This small, observational study aimed to determine if brain fogginess (mental confusion, impaired judgement, poor short-term memory and difficulty concentrating) and intestinal gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). 38 patients presenting with gas and bloating in the absence of short bowel syndrome, and with or without brain fog were assessed. All patients with brain fog were consuming probiotics, with a higher proportion of them diagnosed with SIBO and D-lactic acidosis, when compared to the non-brain fog group. The researchers stopped probiotics in all patients and administered antibiotics, observing a significant reduction in brain fog and gastrointestinal symptoms. Whilst this is a small, observational study, nutrition practitioners may wish to assess the likelihood of SIBO and D-lactic acidosis before recommending probiotics, especially in the presence of brain fog.
Abstract
BACKGROUND D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). METHODS Patients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and blood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed. RESULTS Thirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%). CONCLUSIONS We describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.
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Functional interactions between the gut microbiota and host metabolism.
Tremaroli, V, Bäckhed, F
Nature. 2012;489(7415):242-9
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This literature review aims to discuss evidence for the role of the gut microbiota in metabolism and possible links to obesity. Obesity and caloric intake can influence the microbiota, but whether the reverse is true in humans remains unclear. Much of the mechanisms have been determined in rodents, determining similar pathways in humans is difficult. The interplay of diet, host and gut microbiota may cause increased gut permeability (leaky gut) that could lead to an increase in inflammation that may cause obesity, fatty liver disease and insulin resistance. It is increasingly accepted that gut microbiota can contribute to diseases such as obesity, diabetes and cardiovascular disease, but exactly how and by how much remains unclear. Evidence for treating the microbiota to help with these metabolic diseases, either by pre- or probiotic supplementation, is building. However, double-blind, placebo-controlled studies are required to determine effects. The influence of the gut microbiota is a promising area, but one that needs further research.
Abstract
The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.