Recent insights into the role of microbiome in the pathogenesis of obesity

Abstract

Obesity is a risk factor for many chronic diseases and its rising prevalence the last couple of decades is a healthcare concern in many countries. Obesity is a multifactorial problem that is not only limited in its causation by diet and lack of exercise. Genetics but also environmental factors such as the gut microbiome should similarly be taken into account. A plethora of articles have been published, that from various different angles, attempt to disentangle the complex interaction between gut microbiota and obesity. Examples range from the effect of the gut microbiota on the host immune system to the pathophysiological pathways in which microbial-derived metabolites affect obesity. Various discordant gut microbiota findings are a result of this complexity. In this review, in addition to summarizing the classical role of the gut microbiome in the pathogenesis of obesity, we attempt to view both the healthy and obesogenic effects of the gut microbiota as a consequence of the presence or absence of collective guilds/trophic networks. Lastly, we propose avenues and strategies for the future of gut microbiome research concerning obesity.

The gut microbiome associated with LGI1- and CASPR2-antibody encephalitis

“…The frequency of HLA DRB*07:01 in our cases (91% carriers) matches that observed in cohorts of similar ancestry19,21 , and our AE cases were primarily LGI1 positive (n=43/47) -in keeping with literature To our knowledge this is the first observation linking gut microbiome compositional changes to the major LGI1-Ab-E genetic risk locus. Encouragingly a reduction of the F/B ratio and taxa diversity has been associated in another gut microbiome study ofLGI1-Ab-E in a cohort of 15 patients of Han Chinese ancestry compared to 25 matched controls using 16S rRNA sequencing Although the Chinese investigation did not consider HLA genotypes, together our studies show evidence that a subtle shift in taxa composition measured by the F/B ratio is associated with LGI1-Ab-E and is consistent with an inflammatory disease model That said, for obesity, one of the first traits where the F/B ratio was suggested as a biomarker, results are frequently discrepent 32 and that phyla encompass a wide variety of taxa with differing functional attributes26…”

“…Although the Chinese investigation did not consider HLA genotypes, together our studies show evidence that a subtle shift in taxa composition measured by the F/B ratio is associated with LGI1-Ab-E and is consistent with an inflammatory disease model 48 . That said, for obesity, one of the first traits where the F/B ratio was suggested as a biomarker, results are frequently discrepent 32 and that phyla encompass a wide variety of taxa with differing functional attributes 26 . Wider and further studies are warranted in neuroinflammatory and epilepsy traits, to investigate the veracity of our observation.…”

“…LGI1-antibodies carry specific class-II HLA alleles, namely HLA-DRB1*07:01 (OR: 26 The gut microbiome elegantly provides an interface to explain such an environmental trigger. Indeed, in a variety of autoimmune central nervous system diseases, there is growing evidence for an aetiological link between the gut microbiome and the brain, principally via innate immunity and Tcells [23][24][25] .…”

“…Indeed, in a variety of autoimmune central nervous system diseases, there is growing evidence for an aetiological link between the gut microbiome and the brain, principally via innate immunity and Tcells [23][24][25] . In several autoimmune diseases, skews in gut microbial populations have been discovered which may predispose to the illness 23,[26][27][28] . Further, in autoantigen-specific illnesses, a distinctive microbial signature may provide a similarly elegant link to the LGI1 and CASPR2 autoantigens through molecular mimicry.…”

Positive Regulation of Acetate in Adipocyte Differentiation and Lipid Deposition in Obese Mice

“…This reduces the ability of lipid-oxidative metabolism to occur, and increases the inflammation development of adipose tissue, the secretion of pro-inflammatory adipokines and insulin resistance [3,24]. Evidence has shown that SCFAs affected adipose tissue metabolism [25], particularly acetate, which was the most abundant SCFAs in the body's system. Therefore, this study explored the mechanism of acetate regulating lipid metabolism through the treatment of obese mice on a high-fat diet with acetate via gavage.…”