Modification of fecal microbiota as a mediator of effective weight loss and metabolic benefits following bariatric surgery

ABSTRACT

Introduction

Bariatric surgery (primarily Laparoscopic Sleeve Gastrectomy [LSG] and Roux-en-Y Gastric Bypass [RYGB]) is an efficacious and durable therapeutic option for weight loss in obesity. The mechanisms that mediate weight loss following bariatric surgery remain incompletely understood.

Areas covered

Pubmed search of published data on fecal microbiota, metabolic health, LSG, and RYGB. The fecal microbiome plays a key role in the establishment and maintenance of metabolic wellbeing, and may also contribute (through fecal dysbiosis) to metabolic dysfunction. LSG and RYGB both result in characteristic, procedure-specific changes to the fecal microbiota that may mediate at least some of the resultant weight-loss and metabolically beneficial effects, when applied to the management of obesity.

Expert opinion

The human fecal microbiome, containing around 100 trillion microbes, evolved over millions of years and interacts symbiotically with its human host. Rodent-based studies have provided insights into the complexities of the gut-microbiome-brain axis. This includes the important role of the gut microbiome in the mediation of normal immunological development, inflammatory pathways, metabolic functioning, hypothalamic appetite regulation, and the absorption of essential nutrients as by-products of bacterial metabolism. Fecal transformation is likely to provide an important therapeutic target for future prevention and management of obesity and metabolic dysfunction.

KEYWORDS:

• Fecal microbiota
• obesity
• bariatric surgery
• microbiome
• incretins
• sleeve gastrectomy
• Roux-en-Y gastric bypass

Article highlights

• The human gut microbiome co-evolved with our hominid ancestors over millions of years. Formed of approximately 100 trillion microbes, the gut microbiome vastly outnumbers our own cells. Over recent years, our understanding of the importance of the gut microbiome for health and wellbeing has been transformed.

• Most of the current literature on the effects of gut microbiota (including fecal transplantation) on metabolic health stems from rodent studies. Data from human-based studies on gut microbiota and metabolic health are largely association-based, enabling only tenuous conclusions regarding causality.

• Most of our current data on the gut microbiome relates to individual bacterial species. Certain gut bacterial species such as Enterococcus, Akkermansia muciniphila, and F. prausnitzii have been shown to associate with a favorable metabolic and inflammatory profile. Certain bacterial species release useful by-products of metabolism. For example, Enterococcus, which through fermentation of dietary fibre, releases short-chain fatty acids (SCFAs) that confer metabolic benefits. (SCFA also contributes to around 10% of energy intake in humans, and therefore may potentially contribute to weight gain. The role of SCFAs in the establishment and maintenance of metabolic homeostasis therefore remains controversial) [65,79].

• Some gut bacterial species, such as Bacteroidetes and Firmicutes associate with human obesity.

• Bariatric surgery is our most effective treatment strategy for obesity. The mechanisms of weight loss following bariatric surgery are incompletely understood, although current dogma implicates earlier release of incretins from the distal gut.

• Based on the current literature (primarily studies on RYGB), characteristic modifications to the gut microbiome occur following bariatric surgery, and appear to be procedure-specific and largely metabolically favorable (based on known associations of specific gut bacterial species).

• Future studies should focus on attempts to replicate the characteristic modifications to the gut microbiome that normally occur following bariatric surgery. Such studies on patients with obesity would require transformation of the gut microbiome through, for example, fecal transplantation. Confirmation of established metabolic and appetitive benefits (including weight loss) from such an intervention, would provide a novel and promising therapeutic strategy, that could be implemented potentially on a global level for the prevention and management of obesity and metabolic dysfunction.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.