http://microbecol.khu.ac.kr/PDF_paper/TiB2015.pdf

Proteobacteria: Microbial signature of dysbiosis in gut microbiota

The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.

https://www.tandfonline.com/doi/pdf/10.1080/19490976.2015.1134082

Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

It is widely accepted that obesity and associated metabolic diseases, including type 2 diabetes, are intimately linked to diet. However, the gut microbiota has also become a focus for research at the intersection of diet and metabolic health. Mechanisms that link the gut microbiota with obesity are coming to light through a powerful combination of translation-focused animal models and studies in humans. A body of knowledge is accumulating that points to the gut microbiota as a mediator of dietary impact on the host metabolic status. Efforts are focusing on the establishment of causal relationships in people and the prospect of therapeutic interventions such as personalized nutrition.

/pdf/diet-microbiota-interactions-as-moderators-of-human-2x945rf0pr.pdf

Diet–microbiota interactions as moderators of human metabolism

OBJECTIVE: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans The impact of diet and weight loss on this bacterial species is unknown Our objective was to evaluate the association between faecal A muciniphila abundance, faecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR) DESIGN: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilisation diet in overweight and obese adults (N=49, including 41 women) Faecal A muciniphila abundance, faecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and weight stabilisation RESULTS: At baseline A muciniphila was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter Subjects with higher gene richness and A muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution Individuals with higher baseline A muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR These participants also experienced a reduction in A muciniphila abundance, but it remained significantly higher than in individuals with lower baseline abundance A muciniphila was associated with microbial species known to be related to health CONCLUSIONS: A muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults The interaction between gut microbiota ecology and A muciniphila warrants further investigation TRIAL REGISTRATION NUMBER: NCT01314690

https://gut.bmj.com/content/gutjnl/65/3/426.full.pdf

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.

/pdf/conserved-shifts-in-the-gut-microbiota-due-to-gastric-bypass-32i3genqkl.pdf

Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity

Methods and compositions are provided for treating weight related conditions and metabolic disorders by altering microbiota in a subject. One aspect provides methods and compositions to alter microbiota in a subject by administering to the subject a composition that includes a substantially purified microbiota from phyla such as Bacteroidetes, Proteobacteria, Firmicutes and Verrucomicrobia or orders such as Bacteroidales, Verrucomicrobiales, Clostridiales and Enterobacteriales or genera such as Alistipes, Clostridium, Escherichia, and Akkermansia. Another aspect includes a pharmaceutical composition for altering microbiota that includes a therapeutically effective amount of substantially purified microbiota and a pharmaceutically acceptable carrier. Yet another aspect includes methods for treating a disorder, such as obesity, in a subject in need of such treatment by changing relative abundance of microbiota in a gastrointestinal tract of the subject without or in addition to a surgical procedure.

Compositions of microbiota and methods related thereto

Antibiotic exposure promotes fat gain.

Background: GLP-1 receptor agonist (GLP-1RA) based therapies are effective for treating T2D, however the short half-life of GLP-1 and adverse events associated with pharmacologic dosing limit durable patient outcomes. Local production of GLP-1 in the pancreas could improve beta cell function and health, while limiting systemic administration side effects. Towards this goal, we developed an adeno-associated virus (AAV)-based gene therapy for local GLP-1 production from beta cells. 

Alice P. Liou

Papers

Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity

Compositions of microbiota and methods related thereto

Antibiotic exposure promotes fat gain.

AAV-Mediated Pancreatic Gene Therapy for Type-2 Diabetes