ReviewThe Gut Microbiota as a Mediator of Metabolic Benefits after Bariatric Surgery
Introduction
Obesity and its associated spectrum of metabolic diseases represent a growing problem worldwide (1). For morbidly obese patients, the implementation of lifestyle changes through the combination of a healthful diet, physical activity and behavioural modifications has modest effects on excess fat accumulation and its associated comorbidities 2, 3. Moreover, anti-obesity drugs are costly and offer limited weight loss, which often do not justify their potentially severe adverse effects; indeed, several previously authorized drugs have recently been removed from European and American markets (4). Therefore, bariatric surgery is the only successful strategy for effective and sustained weight loss, reduction of obesity-associated comorbidities and improved lifestyle in morbidly obese people 5, 6.
A link between the gut microbiota and the metabolic health of the host has been uncovered 7, 8 and, although far from being completely understood, it is opening avenues for the development of novel treatments and metabolic disease biomarkers. Because bariatric surgery is based on drastic physiologic and anatomic changes in the gastrointestinal tract, which include major shifts in gut microbial communities, there is a growing interest in understanding which changes in the gut microbiota could underpin the benefits of metabolic surgery and lead to improved glycemic control and fat-mass loss. In this review, we summarize and discuss the most recent data concerning the role of the gut microbiota in bariatric surgery.
Section snippets
Overview of Bariatric Surgery
Bariatric surgical procedures can be classified into 3 major categories according to their mechanisms of action: 1) restrictive, which consists of limiting food intake by decreasing the stomach's natural capacity, such as laparoscopic adjustable gastric banding and laparoscopic sleeve gastrectomy (LSG), also known as vertical sleeve gastrectomy (VSG)); 2) malabsorptive, in which the principal aim is to bypass a portion of the small intestine so that nutrient absorption is decreased and 3) a
Is There a Dark Side to the Gut Microbiota after Bariatric Surgery?
Trimethylamine-N-oxide (TMAO) is synthesized in the liver by a reaction catalyzed by the enzyme flavin monooxygenase, and its substrate is trimethylamine (TMA), a product generated exclusively by the gut microbiota from dietary choline, phosphatidylcholine, L-carnitine or gamma-butyrobetaine. There is strong evidence that circulating TMAO is linked to atherogenesis and major adverse cardiovascular events 39, 40, 41, 42, but the mechanism is not yet well understood. Although animal studies have
Bariatric Surgery and Glycemic Control
Following RYGB surgery, complete remission of type 2 diabetes is seen in approximately 80% of patients, whereas another 15% have a substantial improvement but still need antidiabetes drugs to improve glycemic control (57). There is compelling evidence that the underlying mechanisms of improved glycemic control are beyond the influence of weight reduction because improved glucose tolerance and insulin sensitivity are short-term traits often observed within days after bariatric surgery, prior to
Gut Microbiota, Bile Acids and Bariatric Surgery
BAs are synthesized in the liver from cholesterol and then stored in the gallbladder. Primary BAs are produced in the liver, and most of them are secreted into the bile and conjugated into glycine or taurine. When in contact with the intestinal bacteria, BAs undergo 7α-dehydroxylation and glycine/taurine deconjugation, yielding secondary BAs. Upon ingestion of a meal, I cells, which are present mostly in the duodenum and in the jejunum, secrete cholecystokinin to then trigger pancreatic
Limitations in the methods applied to assess the impact of bariatric surgery on gut microbiota
The studies described in Table 1 and Table 2 used methodologies based on taxa-targeted qPCR or metagenomics (16S rRNA gene-based analysis or shotgun sequencing from genomic DNA) from stool samples, which enables a more comprehensive understanding of shifts occurring in the structure and function of gut microbial communities after surgery. However, general limitations in applying metagenomics for studying gut microbiome or other ecosystems have been well described and may influence the results
Conclusions
Bariatric surgery induces major anatomic rearrangements in the gastrointestinal system, leading to drastic functional and taxonomic changes in gut microbial communities, which are positioned to be a mechanism involved in the rapid improvements in glycemic control and marked weight loss over the long term. This constitutes an unprecedented model for investigating new molecular targets in the host (e.g. FXR and TGR5), small molecules of microbial origin and even new probiotic strains to fight
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