Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial

Mocanu, Valentin; Zhang, Zhengxiao; Deehan, Edward C.; Kao, Dina; Hotte, Naomi; Karmali, Shahzeer; Birch, Daniel W.; Samarasinghe, Kalutota K.; Walter, Jens; Madsen, Karen

doi:10.1038/s41591-021-01399-2

Cited by 172 publications

(138 citation statements)

References 51 publications

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“…In another study, daily cellulose supplementation after a single-dose oral FMT in individuals with metabolic syndrome improved insulin sensitivity 6 weeks after treatment compared to baseline. The authors found that this outcome was linked to higher GLP-1 secretion and better engraftment of the donor microbiota; however, they did not report significant changes for either the proportions of butyrate producers or fecal butyrate levels ( 109 ). Overall, the studies on FMT indicate that, while this procedure may improve insulin sensitivity in the short-term, the host gut microbiota is resilient enough to drift away the foreign microbial community in the long-term.…”

Section: Restoration Of Butyrate In Type 2 Diabetesmentioning

confidence: 99%

Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes

Arora

Tremaroli

2021

Front. Endocrinol.

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Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.

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Section: Restoration Of Butyrate In Type 2 Diabetesmentioning

confidence: 99%

Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes

Arora

Tremaroli

2021

Front. Endocrinol.

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“…Similarly, the blood glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) index and inflammation were significantly reduced by probiotic intervention in a randomized double-blind placebo-controlled study of 61 Saudi T2DM patients (26). Recently, Mocanu et al found that fecal microbiota transplantation (FMT) combined with low-fermentable fibers interventions regulated gut microbiota and improved HOMA2-IR and insulin sensitivity of obesity and metabolic syndrome patients (27). Therefore, gut microbiota dysbiosis is associated with T2DM, and gut microbial modulation is likely an effective strategy to improve T2DM by precision supplement of probiotics and even FMT.…”

Section: Introductionmentioning

confidence: 99%

Gut Bacterial Characteristics of Patients With Type 2 Diabetes Mellitus and the Application Potential

Que

Cao

et al. 2021

Front. Immunol.

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Type 2 diabetes mellitus (T2DM) is a complex disorder comprehensively influenced by genetic and environmental risk, and research increasingly has indicated the role of microbial dysbiosis in T2DM pathogenesis. However, studies comparing the microbiome characteristics between T2DM and healthy controls have reported inconsistent results. To further identify and describe the characteristics of the intestinal flora of T2DM patients, we performed a systematic review and meta-analysis of stool microbial profiles to discern and describe microbial dysbiosis in T2DM and to explore heterogeneity among 7 studies (600 T2DM cases, 543 controls, 1143 samples in total). Using a random effects model and a fixed effects model, we observed significant differences in beta diversity, but not alpha diversity, between individuals with T2DM and controls. We identified various operational taxonomic unit (OTUs) and bacterial genera with significant odds ratios for T2DM. The T2DM signatures derived from a single study by stepwise feature selection could be applied in other studies. By training on multiple studies, we improved the detection accuracy and disease specificity for T2DM. We also discuss the relationship between T2DM-enriched or T2DM-depleted genera and probiotics and provide new ideas for diabetes prevention and improvement.

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“…Whether or not a consistent association between the microbiota and obesity phenotypes exists, another important, but unresolved, question is whether or not the human gut microbiome contributes directly to changes in weight after an intervention, independent of baseline BMI. While the gut microbiome has been shown to contribute to weight gain in mice ( 8 , 9 ), it remains unclear whether similar factors might contribute to weight loss ( 10 ) and whether or not these results would translate well to humans ( 11 , 12 ). Recent feeding studies have shed some light on this issue, demonstrating that humans with higher Prevotella -to- Bacteroides ratios tend to lose significantly more weight on a high-fiber diet, particularly individuals with low salivary amylase levels ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans

et al. 2021

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Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to dietary interventions, but the exact functional determinants underlying this phenomenon remain unclear. In this study, we set out to better understand interactions between baseline BMI, metabolic health, diet, gut microbiome functional profiles, and subsequent weight changes in a human cohort that underwent a healthy lifestyle intervention.

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Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial

Cited by 172 publications

References 51 publications

Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes

Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes

Gut Bacterial Characteristics of Patients With Type 2 Diabetes Mellitus and the Application Potential

Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans

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