What Is in the Gut?

The human gut microbiota is primarily made up of bacterial organisms residing in the colon, with a smaller percentage of Archaea, eukaryotes, and viruses. The 2 major bacterial-dominant phyla in the human gut include Firmicutes and Bacteriodetes, followed by Proteobacteria and Actinobacteria, which altogether account for 97% of the gut microbe population.3 A greater percentage of body fat correlates with a greater ratio of Firmicutes to Bacteroidetes; hence, obesity is associated with changes in the amount of at least 2 of these major phyla.9 Generally, Bacteriodetes are decreased and Firmicutes are increased in obesity, resulting in an increased Firmicutes-to-Bacteriodetes ratio (Table).

A number of small studies have found controversial and conflicting results regarding the optimal microbiota profile and the different phenotypes associated with BMI. This is most likely the result of the various less-abundant species of each phylum, different methodologies employed in each study, and an increase in more recent data and knowledge.10

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Although current evidence is preliminary, multiple factors including genetic, environmental, diet, exercise, and psychological stress are considered to contribute to the incidence of obesity.Jayasinghe and colleagues identified the connection between obesity and metabolic disorders in relation to the potential of FMT as a treatment for obesity. Gut microbiota were found to affect host metabolism by promoting uptake of monosaccharides, storage of triglycerides, digestion of dietary fiber, and the synthesis of hormonal precursors.11

Short-chain fatty acids (SCFA) are microbial metabolites responsible for several physiologic effects. Complex carbohydrates are metabolized by intestinal microbiota to oligosaccharides and monosaccharides, and then fermented to SCFA such as butyrate, propionate, and acetate.12 Once absorbed in the colon, propionate and acetate act as substrates in the liver and peripheral organs for gluconeogenesis and lipogenesis. SCFA reduce intestinal permeability and regulate such processes within the gastrointestinal tract as absorption of water and electrolytes. The types and amount of SCFA produced are determined by how much carbohydrate is consumed and the composition of the gut microbiota. A higher number of SCFA is associated with obesity due to the increased dietary energy harvest, which translates to more calories absorbed from the diet compared with a lower amount of SCFA.

Two important points to recognize are that obesity is associated with microbial dysbiosis, characterized by decreased microbial gut diversity and lack of bacterial richness, and that lean individuals have a more diverse gut microbiome and more optimal metabolic homeostasis.13

Multiple factors contribute to the composition of the gut microbiome, dysbiosis, and fecal microbiota diversity. These variables result in a lack of consistency in an obese individuals’ microbiota composition and complicating the relationship between gut microbiota and energy homeostasis. Allen et al established a relationship between exercise and changes in the gut microbiota.14 This small study of 32 lean and obese individuals reported the presence of a more diverse gut microbiota with regular exercise, which was sustained only if exercise continued. A study by Graessler et al evaluated patients following bariatric surgery and found increased microbial diversity during weight loss that was not sustained in those gaining weight 2 years following the procedure.15  De Clercq and colleagues introduced the role of the gut-brain axis and microbial diversity in metabolism.16 The investigators highlighted the link between host metabolism and behavior via bidirectional signaling between the gastrointestinal tract and the brain.

The effect of SCFA on energy homeostasis through the regulation of gastrointestinal hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin has also been the focus of research. Preclinical studies show that modifying the microbiota of rodents through FMT results in alterations of these hormones, which affect not only metabolism but also behavior. Whether these findings translate to human metabolism is as yet unclear. However, the ideal microbiome may have the potential to command the gut-brain axis and positively influence the pathophysiology of metabolic disease.