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Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.
Wastyk, HC, Perelman, D, Topf, M, Fragiadakis, GK, Robinson, JL, Sonnenburg, JL, Gardner, CD, Sonnenburg, ED
Gut microbes. 2023;15(1):2178794
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Rates of metabolic syndrome are high throughout developed countries. Metabolic syndrome is a cluster of conditions that occur together and increase your risk for heart disease, stroke, and type 2 diabetes. Studies in animals and humans have shown that the composition of the gut microbiome may be linked to metabolic syndrome and that it is affected by diet. This randomised control trial of 39 individuals showed that the supplementation of a probiotic containing three different probiotic strains did not have a population wide effect but did influence a subset of individuals. These individuals had a different microbiome by the end of the trial and a decrease in blood pressure and blood lipids. Interestingly these individuals also had a higher dietary intake of sugar, yet a lower blood sugar level. It was concluded that the response to probiotic supplements may be dependent upon an individual’s diet. This study could be used by healthcare professionals to understand that diet may influence the success of probiotics, however more research is warranted before firm conclusions are made on the optimal diet during supplementation.
Abstract
An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.
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Influence of Prolonged Whole Egg Supplementation on Insulin-like Growth Factor 1 and Short-Chain Fatty Acids Product: Implications for Human Health and Gut Microbiota.
Suta, S, Ophakas, S, Manosan, T, Honwichit, O, Charoensiddhi, S, Surawit, A, Pongkunakorn, T, Pumeiam, S, Mongkolsucharitkul, P, Pinsawas, B, et al
Nutrients. 2023;15(22)
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Eggs have been shown to be a rich source of several vitamins and minerals and that increased consumption improves growth and prevents stunting in children, however the mechanism behind this is not fully understood. This randomised control trial of 75 children aged 8-14 years aimed to determine the effect of prolonged egg supplementation on insulin-like growth factor 1 (IGF-1), which is involved in bone development and the production of metabolites known as short-chain fatty acids (SCFAs) by gut microbiota. The results showed that consuming 10 additional whole eggs per week in addition to their usual egg consumption for 35 weeks resulted in increased IGF-1 levels compared to control. The production of SCFAs remained the same with whole egg supplementation as with control. The production of IGF-1 was associated with the production of the beneficial SCFAs propionate, butyrate, isovalerate, and valerate. Interestingly however, the consumption of whole eggs also increased the production of some gut microbiota associated metabolites, which have been shown to have adverse health effects. It was concluded that increased whole egg consumption may promote bone health and growth in children and that the association between IGF-1 and SCFAs indicates a connection between diet, microbiota, and health. This study could be used by healthcare professionals to consider the recommendation of increased egg consumption in children to promote bone health and growth. It should be noted that the children used in this study were from rural Thailand, where undernourishment may be an issue.
Abstract
The gut microbiota exert a profound influence on human health and metabolism, with microbial metabolites playing a pivotal role in shaping host physiology. This study investigated the impact of prolonged egg supplementation on insulin-like growth factor 1 (IGF-1) and circulating short-chain fatty acids (SCFAs). In a subset of a cluster-randomized trial, participants aged 8-14 years were randomly assigned into three groups: (1) Whole Egg (WE)-consuming 10 additional eggs per week [n = 24], (2) Protein Substitute (PS)-consuming yolk-free egg substitute equivalent to 10 eggs per week [n = 25], and (3) Control Group (C) [n = 26]. At week 35, IGF-1 levels in WE significantly increased (66.6 ± 27.7 ng/mL, p < 0.05) compared to C, with positive SCFA correlations, except acetate. Acetate was stable in WE, increasing in PS and C. Significant propionate differences occurred between WE and PS (14.8 ± 5.6 μmol/L, p = 0.010). WE exhibited notable changes in the relative abundance of the Bifidobacterium and Prevotella genera. Strong positive SCFA correlations were observed with MAT-CR-H4-C10 and Libanicoccus, while Roseburia, Terrisporobacter, Clostridia_UCG-014, and Coprococcus showed negative correlations. In conclusion, whole egg supplementation improves growth factors that may be related to bone formation and growth; it may also promote benefits to gut microbiota but may not affect SCFAs.
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Advancements in Nutritional Strategies for Gestational Diabetes Management: A Systematic Review of Recent Evidence.
Sánchez-García, JC, Saraceno López-Palop, I, Piqueras-Sola, B, Cortés-Martín, J, Mellado-García, E, Muñóz Sánchez, I, Rodríguez-Blanque, R
Journal of clinical medicine. 2023;13(1)
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Gestational Diabetes Mellitus (GDM) causes hyperglycaemia due to the deficit of insulin during pregnancy. Dietary and lifestyle management plays a vital role in maintaining glycaemic control in women with GDM to avoid health risks to the mother and baby. Therefore, this systematic review of fourteen randomised controlled trials evaluated the latest research advancements to identify effective nutritional strategies for managing hyperglycaemia in women with GDM. Among all the dietary strategies implemented in the included randomised controlled trials, probiotic supplementation and supplementation of probiotics and vitamin D were most effective in GDM. Further robust studies are required to evaluate the potential effectiveness of different nutritional strategies for managing GDM. Healthcare professionals can use the results of this systematic review to understand the latest evidence supporting nutritional strategy for women with GDM and the need for personalised support for managing hyperglycaemia in GDM.
Abstract
Gestational diabetes mellitus (GDM) is defined as hyperglycaemia first detected at any time during pregnancy with values lower than those determined by the WHO for diabetes diagnosis in adults. This pathology, with a worldwide prevalence of 13.4%, causes significant maternal and foetal risks. The first line of treatment consists of maintaining normo-glycaemia through an adequate diet and lifestyle changes. The aim is to synthesize the scientific evidence updating the nutritional recommendations for the effective management of GDM. A systematic review of the scientific literature was conducted following the PRISMA guidelines. Randomized clinical trials published within the last five years and providing information on nutritional recommendations to achieve an effective management of gestational diabetes were selected. The databases searched were PubMed, the WOS Core Collection, SCOPUS, and CINAHL, using the MeSH terms: "Diabetes, Gestational"; "Nutrition Assessment (nutrition*)"; "Diet"; "Eating"; and "Food"; with the Boolean operators "AND" and "OR". The PEDro scale (Physiotherapy Evidence Database) was used to assess the scientific quality of the studies, with a mean score of 8.9, indicating an average good scientific quality. Results: A total of 809 papers were collected, of which, after applying the inclusion and exclusion criteria, 14 randomized clinical trials were selected. Probiotic supplementation and co-supplementation with vitamin D have been found to be the most beneficial options for both mothers with GDM and neonates, but the most effective regimens are not known. Diets enriched with extra virgin olive oil (EVOO) and oat bran, as well as some recommendations focused on carbohydrates also seem effective, as well as diets designed for this group of women with GDM such as "CHOICE". Conclusions: Although there are numerous proposals that have been published in recent years focused on the diet of women with GDM in order to improve their results and those of their children, it is the supplementation with probiotics and the co-supplementation with vitamin D that is most agreed upon as beneficial; however, more research is needed into which protocols are most effective. Other proposals that could also be beneficial should be further studied.
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The Roles of Probiotics in the Gut Microbiota Composition and Metabolic Outcomes in Asymptomatic Post-Gestational Diabetes Women: A Randomized Controlled Trial.
Hasain, Z, Raja Ali, RA, Ahmad, HF, Abdul Rauf, UF, Oon, SF, Mokhtar, NM
Nutrients. 2022;14(18)
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Gestational Diabetes Mellitus (GDM) happens to some pregnant women during the second and third trimester of their pregnancy, increasing the risk of developing Type 2 Diabetes Mellitus by 10-fold later in life. Aberrant changes to the gut microbial composition in pregnant gestational diabetic women are found to have a negative effect on the metabolism that may carry on to the postpartum period. On the other hand, probiotics may have a host metabolism modifying effect by reducing inflammation and gut dysbiosis in asymptomatic post-GDM women. This 12-week randomised, double-blinded, controlled, parallel-group clinical trial looked at the effect of probiotic supplementation on inflammatory and metabolic outcomes in asymptomatic post-GDM women. The one hundred and thirty-two participants were randomised to receive either a probiotic formulation containing Lactobacillus and Bifidobacterium stains or a placebo. Participants in the probiotic group showed a significant improvement in fasting blood glucose, HbA1c, total cholesterol, triglycerides and high-sensitivity C-reactive protein compared to the placebo group. In addition, the probiotic supplementation led to an increase in Bifidobacterium adolescentis. Healthcare professionals can use the results of this study to understand the beneficial effects of probiotic supplements in post-GDM women. However, further robust studies are required to evaluate the functions of probiotic supplements in post-GDM women from different backgrounds.
Abstract
Probiotics are widely used as an adjuvant therapy in various diseases. Nonetheless, it is uncertain how they affect the gut microbiota composition and metabolic and inflammatory outcomes in women who have recently experienced gestational diabetes mellitus (post-GDM). A randomized, double-blind, placebo-controlled clinical trial involving 132 asymptomatic post-GDM women was conducted to close this gap (Clinical Trial Registration: NCT05273073). The intervention (probiotics) group received a cocktail of six probiotic strains from Bifidobacterium and Lactobacillus for 12 weeks, while the placebo group received an identical sachet devoid of living microorganisms. Anthropometric measurements, biochemical analyses, and 16S rRNA gene sequencing results were evaluated pre- and post-intervention. After the 12-week intervention, the probiotics group's fasting blood glucose level significantly decreased (mean difference -0.20 mmol/L; p = 0.0021). The HbA1c, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly different between the two groups (p < 0.05). Sequencing data also demonstrated a large rise in the Bifidobacterium adolescentis following probiotic supplementation. Our findings suggest that multi-strain probiotics are beneficial for improved metabolic and inflammatory outcomes in post-GDM women by modulating gut dysbiosis. This study emphasizes the necessity for a comprehensive strategy for postpartum treatment that includes probiotics to protect post-GDM women from developing glucose intolerance.
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The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.
Rinott, E, Meir, AY, Tsaban, G, Zelicha, H, Kaplan, A, Knights, D, Tuohy, K, Scholz, MU, Koren, O, Stampfer, MJ, et al
Genome medicine. 2022;14(1):29
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The Mediterranean (MED) diet, high in nuts, vegetables, and legumes and low in red meat intake, is recommended for the prevention of cardiometabolic diseases. It has been reported that adherence to MED dietary patterns is associated with a distinct gut microbiome profile. The main aim of this study was to investigate the effect of MED-based dietary interventions on the gut microbiome composition and function. This study was focused on the analysis of the DIRECT-PLUS trials’ secondary outcomes, including gut microbiome profile, lipid profile, glycaemic control, inflammatory state, and cardiometabolic risk. All eligible participants were randomised in a 1:1:1 ratio, into one of the three intervention groups: healthy dietary guidelines (HDG), MED, and Green-MED, all combined with physical activity accommodation. Results showed that: - the Green-MED diet [an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake] induced a prominent change in the gut microbiome composition, driven by the low-prevalent “non-core” fraction of the gut microbiome. - the MED and Green-MED diets improved cardiometabolic markers. These beneficial changes in levels of cardiometabolic biomarkers were associated with a concurrent shift in the gut microbiome composition. Authors conclude that the Green-MED diet has extensive effects on the composition and function of the host gut microbiome, with the latter partially mediating the beneficial effects of the diet on cardiometabolic health.
Abstract
BACKGROUND Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. METHODS In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. RESULTS Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. CONCLUSIONS Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. TRIAL REGISTRATION The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.
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A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease.
Cheng, R, Wang, L, Le, S, Yang, Y, Zhao, C, Zhang, X, Yang, X, Xu, T, Xu, L, Wiklund, P, et al
Nature communications. 2022;13(1):2555
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Non-alcoholic fatty liver disease (NAFLD) is a common chronic disease that is associated with the development of type 2 diabetes (T2D). A commonality between the two diseases is the body’s inefficiency to uptake sugar from the blood, known as insulin resistance. Dysbiosis of the gut microbiota has been shown to be involved in NAFLD and T2D. Exercise and dietary modifications have been shown to increase gut microbiota diversity altering the composition, however the extent of this change is poorly understood. This randomised control trial of 115 individuals with NAFLD and insulin resistance aimed to determine the effects of aerobic exercise and a diet comprising of 37-40% carbohydrate, 35-37% fat, and 25-27% protein on gut microbiota diversity, liver fat content and sugar metabolism. The results showed that generally diet and exercise increased gut microbiota diversity and ensured maintenance of gut microbiota associated with healthy outcomes. Liver fat content was decreased the most with diet and exercise and by nearly 50% but not all subjects responded the same with responders and non-responders identified. It was concluded that there is a necessity for personalisation of diet and exercise programmes for the treatment of NAFLD. This study could be used by healthcare professionals to understand that gut microbiota diversity may be improved by diet and exercise, however not everyone may be similarly affected. Until more is understood about the gut microbiota, it may be necessary to try different diet and exercise regimes, which are optimal for each individual.
Abstract
Exercise and diet are treatments for nonalcoholic fatty liver disease (NAFLD) and prediabetes, however, how exercise and diet interventions impact gut microbiota in patients is incompletely understood. We previously reported a 8.6-month, four-arm (Aerobic exercise, n = 29; Diet, n = 28; Aerobic exercise + Diet, n = 29; No intervention, n = 29) randomized, singe blinded (for researchers), and controlled intervention in patients with NAFLD and prediabetes to assess the effect of interventions on the primary outcomes of liver fat content and glucose metabolism. Here we report the third primary outcome of the trial-gut microbiota composition-in participants who completed the trial (22 in Aerobic exercise, 22 in Diet, 23 in Aerobic exercise + Diet, 18 in No Intervention). We show that combined aerobic exercise and diet intervention are associated with diversified and stabilized keystone taxa, while exercise and diet interventions alone increase network connectivity and robustness between taxa. No adverse effects were observed with the interventions. In addition, in exploratory ad-hoc analyses we find that not all subjects responded to the intervention in a similar manner, when using differentially altered gut microbe amplicon sequence variants abundance to classify the responders and low/non-responders. A personalized gut microbial network at baseline could predict the individual responses in liver fat to exercise intervention. Our findings suggest an avenue for developing personalized intervention strategies for treatment of NAFLD based on host-gut microbiome ecosystem interactions, however, future studies with large sample size are needed to validate these discoveries. The Trial Registration Number is ISRCTN 42622771.
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Effects of a Low-Fat Vegan Diet on Gut Microbiota in Overweight Individuals and Relationships with Body Weight, Body Composition, and Insulin Sensitivity. A Randomized Clinical Trial.
Kahleova, H, Rembert, E, Alwarith, J, Yonas, WN, Tura, A, Holubkov, R, Agnello, M, Chutkan, R, Barnard, ND
Nutrients. 2020;12(10)
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Gut bacteria composition can have an important role in health. Long-term adherence to a plant-based diet can lead to altered gut bacteria compared to omnivores, however how this association is linked to body metabolism is not entirely understood. This randomised control trial of 168 overweight individuals on a vegan diet compared to a control group where individuals followed their usual diet containing animal products, aimed to assess gut microbiota changes and how this may be related to body weight, body composition and the body’s ability to balance blood sugars, over 16 weeks. The results showed that body weight was decreased in the vegan group compared to control group, mainly due to reduced fat mass. Measures of the body’s ability to balance blood sugars was significantly improved in the vegan group. Gut microbiota diversity remained unchanged in the vegan group yet increased in the control group. Several species changes were observed in the vegan and control groups. Faecalibacterium prausnitzii increased in the vegan group and this was related to decreases in body weight and fat mass. A smaller decrease in Bacteroides fragilis compared to control was observed with a low-fat vegan diet and this was also associated to decreased body weight, fat mass and increased blood sugar control. It was concluded that changes in body weight, body composition and the body’s ability to balance blood sugars in overweight adults following a vegan diet are related to gut microbiota changes. This study could be used by healthcare professionals to recommend a vegan diet to overweight adults to aid weight loss and understand how this diet may affect those changes.
Abstract
Diet modulates gut microbiota and plays an important role in human health. The aim of this study was to test the effect of a low-fat vegan diet on gut microbiota and its association with weight, body composition, and insulin resistance in overweight men and women. We enrolled 168 participants and randomly assigned them to a vegan (n = 84) or a control group (n = 84) for 16 weeks. Of these, 115 returned all gut microbiome samples. Gut microbiota composition was assessed using uBiome Explorer™ kits. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was quantified with the predicted clamp-derived insulin sensitivity index from a standard meal test. Repeated measure ANOVA was used for statistical analysis. Body weight decreased in the vegan group (treatment effect -5.9 kg [95% CI, -7.0 to -4.9 kg]; p < 0.001), mainly due to a reduction in fat mass (-3.9 kg [95% CI, -4.6 to -3.1 kg]; p < 0.001) and in visceral fat (-240 cm3 [95% CI, -345 to -135 kg]; p < 0.001). PREDIcted M, insulin sensitivity index (PREDIM) increased in the vegan group (treatment effect +0.83 [95% CI, +0.48 to +1.2]; p < 0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (+5.1% [95% CI, +2.4 to +7.9%]; p < 0.001) and correlated negatively with changes in weight (r = -0.24; p = 0.01), fat mass (r = -0.22; p = 0.02), and visceral fat (r = -0.20; p = 0.03). The relative abundance of Bacteroides fragilis decreased in both groups, but less in the vegan group, making the treatment effect positive (+18.9% [95% CI, +14.2 to +23.7%]; p < 0.001), which correlated negatively with changes in weight (r = -0.44; p < 0.001), fat mass (r = -0.43; p < 0.001), and visceral fat (r = -0.28; p = 0.003) and positively with PREDIM (r = 0.36; p < 0.001), so a smaller reduction in Bacteroides fragilis was associated with a greater loss of body weight, fat mass, visceral fat, and a greater increase in insulin sensitivity. A low-fat vegan diet induced significant changes in gut microbiota, which were related to changes in weight, body composition, and insulin sensitivity in overweight adults, suggesting a potential use in clinical practice.
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Protective effect of probiotics in patients with non-alcoholic fatty liver disease.
Cai, GS, Su, H, Zhang, J
Medicine. 2020;99(32):e21464
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Non-alcoholic fatty liver disease (NAFLD) is common in people with obesity and is characterised by high amounts of fat stored in the liver. Diet and exercise are the standard treatments, however recent studies have indicated that the gut microbiota may have an important role. This randomised control trial of 140 patients with NAFLD, aimed to assess the effect of probiotics when added to standard therapy for 3 months. The results showed that although gut microbiota, some aspects of liver function, blood lipids and blood sugars were all improved in individuals on standard therapy, there were additional improvements in those on standard therapy plus probiotics. It was concluded that although standard therapy alone is adequate to improve NAFLD, probiotics plus standard therapy was superior to standard therapy alone and effective in treatment of NAFLD. This study could be used by health professionals to justify the addition of probiotics to standard therapy to further improve NAFLD outcomes.
Abstract
To investigate the effects of probiotics on liver function, glucose and lipids metabolism, and hepatic fatty deposition in patients with non-alcoholic fatty liver disease (NAFLD).Totally 140 NAFLD cases diagnosed in our hospital from March 2017 to March 2019 were randomly divided into the observation group and control group, 70 cases in each. The control group received the diet and exercise therapy, while the observation group received oral probiotics based on the control group, and the intervention in 2 groups lasted for 3 months. The indexes of liver function, glucose and lipids metabolism, NAFLD activity score (NAS), and conditions of fecal flora in 2 groups were compared before and after the treatment.Before the treatment, there were no significant differences on alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), total bilirubin (TBIL), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), NAFLD activity score (NAS), and conditions of fecal flora in 2 groups (P > .05). After the treatment, ALT, AST, GGT, TC, TG, HOMA-IR, NAS, and conditions of fecal flora in the observation group were better than those in the control group, and the observation group was better after treatment than before. All these above differences were statistically significant (P < .05).Probiotics can improve some liver functions, glucose and lipids metabolism, hepatic fatty deposition in patients with NAFLD, which will enhance the therapeutic effects of NAFLD.
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Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.
Meslier, V, Laiola, M, Roager, HM, De Filippis, F, Roume, H, Quinquis, B, Giacco, R, Mennella, I, Ferracane, R, Pons, N, et al
Gut. 2020;69(7):1258-1268
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Evidence suggests that the Mediterranean diet (MD) may help prevent cardiovascular disease (CVD). However, this could be influenced by an individual’s gut microbiome, highlighting a need for personalised nutrition practices. This randomised crossover control trial aimed to evaluate an 8-week personalised MD intervention in 82 overweight and obese subjects, who were at high risk of cardiovascular disease. The results showed that a personalised MD lowered cholesterol, regardless of the amount of energy consumed and the amount of exercise performed and relied upon adherence to the MD. Gut microbiome composition was altered by a MD and although markers for diabetes were not improved overall, there was an improvement in prediabetes in individuals with higher levels of Bacteroides species and lower levels of Prevotella species. It was concluded that a MD may reduce cholesterol and alter the gut microbiome to benefit cardiovascular health. Health professionals could use this study to switch patients to a MD whilst maintaining their energy intake to reduce cardiovascular risk. In order to see maximum benefit, it would be recommended to take a personalised approach and analyse an individual’s gut microbiome in order to tailor recommendations.
Abstract
OBJECTIVES This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease. DESIGN Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period. RESULTS Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa. CONCLUSION Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
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Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.
Leong, KSW, Jayasinghe, TN, Wilson, BC, Derraik, JGB, Albert, BB, Chiavaroli, V, Svirskis, DM, Beck, KL, Conlon, CA, Jiang, Y, et al
JAMA network open. 2020;3(12):e2030415
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Obesity has become a global pandemic even in adolescents. Lifestyle interventions have had limited impact on this cohort and drugs targeting obesity are often unlicensed in children. The gut microbiome has a role in weight regulation and may be a new target in adolescents with obesity. This randomised control trial of 87 adolescents with obesity over 26 weeks, aimed to assess if faecal microbiome transfer (FMT), which is a method whereby faecal matter is transplanted from one person to another, can be used to treat obesity. The results showed that FMT did not have an effect on body mass index (BMI) and the intervention group had a marginally increased BMI after FMT. Other disorders associated with obesity such as blood sugar levels were also unaffected by FMT, however there was a reduction in fat storage around the middle. It was concluded that FMT alone is not adequate to improve obesity in adolescents, but may reduce fat stored around the middle. Healthcare professionals could use this study to understand that simply transplanting one person’s gut microbiome to another, may not be enough. Targeted personalised approaches may be required, however further research is needed.
Abstract
Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.