The microbiome has received increasing attention over the last 15 years. Although gut microbes have been explored for several decades, investigations of the role of microorganisms that reside in the human gut has attracted much attention beyond classical infectious diseases. For example, numerous studies have reported changes in the gut microbiota during not only obesity, diabetes, and liver diseases but also cancer and even neurodegenerative diseases. The human gut microbiota is viewed as a potential source of novel therapeutics. Between 2013 and 2017, the number of publications focusing on the gut microbiota was, remarkably, 12 900, which represents four-fifths of the total number of publications over the last 40 years that investigated this topic. This review discusses recent evidence of the impact of the gut microbiota on metabolic disorders and focus on selected key mechanisms. This review also aims to provide a critical analysis of the current knowledge in this field, identify putative key issues or problems and discuss misinterpretations. The abundance of metagenomic data generated on comparing diseased and healthy subjects can lead to the erroneous claim that a bacterium is causally linked with the protection or the onset of a disease. In fact, environmental factors such as dietary habits, drug treatments, intestinal motility and stool frequency and consistency are all factors that influence the composition of the microbiota and should be considered. The cases of the bacteria Prevotella copri and Akkermansia muciniphila will be discussed as key examples.

https://gut.bmj.com/content/gutjnl/67/9/1716.full.pdf

Human gut microbiome: hopes, threats and promises

Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the recently identified mechanisms that showcase the role of the intestinal microbiota and barrier dysfunction in metabolic inflammation. We propose a concept by which the gut microbiota fuels metabolic inflammation and dysregulation. Here, the authors describe how metabolic disorders, such as type 2 diabetes and nonalcoholic fatty liver disease, are driven by alterations in the composition of the intestinal microbiota and its metabolites, which translocate from the gut across a disrupted intestinal barrier and contribute to metabolic inflammation.

The intestinal microbiota fuelling metabolic inflammation

GPCR-Mediated Signaling of Metabolites

The Intestinal Immune System in Obesity and Insulin Resistance.

Objectives Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes. Design Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included. Results Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate , 3-methoxyphenylacetic acid and L-histidine ) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients. Conclusions We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity. Trial registration number NCT01454232.

https://gut.bmj.com/content/gutjnl/68/1/70.full.pdf

Milena Monteiro-Sepulveda

Papers

Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling