Microbial modulation of host body composition and plasma metabolic profile

Abstract

The gut microbiota is a critical mediator of nutrition and disease risk. Like most complex traits, the microbiome is under genetic regulation and differs between inbred strains of mice. We tested the effect of fecal microbiota transplantation (FMT) on obesity, and plasma glucose. For this study, we collected microbiota from 2 inbred strains of mice which differ in adiposity and glucose tolerance, C57BL/6J and WSB/EiJ. C57BL/6J female mice (n = 18) were first treated with antibiotics for 4 weeks to ablate the microbiota. Following ablation, the mice were transplanted with microbiota from a C57BL/6J or a WSB/ EiJ mouse and clinical traits and plasma metabolomic profiles were interrogated at 2-and 4-weeks post-transplantation. Unexpectedly, the mice receiving WSB/EiJ microbiota increased adiposity but decreased plasma glucose. Metabolomic and 16S microbiota profiling indicated broad metabolic changes occurred during and after FMT. Detailed analysis of these interactions demonstrated specific microbiota-host metabolite interactions which may alter disease susceptibility.Bacteria is heavily colonized in the gastrointestinal tract, often referred to as the gut microbiota (hereafter referred to as microbiota), which can modulate nutritional status, health, and diseases of the host 1 . The diversity and composition of the gut bacteria have been intensely studied, as well as the microbiota's impact on the health status of the host 2 . The microbiota has been found to be associated with susceptibility to multiple diseases including: obesity 3 , cardiovascular diseases 4 , renal diseases 5 , and metabolic syndrome (MetSyn) 6 , all of which have impact on major public health. For example, 32% of American adults are obese 7 and nearly 35% have MetSyn 8 and the prevalence of these diseases are increasing. However, there are still critical gaps in our knowledge regarding how alterations of the microbiota (dysbiosis) can alter metabolism and thus disease susceptibility. A better understanding of the effect of host genetic-microbiota interactions on the composition of the microbiota and disease susceptibility is needed. A holistic view of the metabolic status of an individual, including both microbiota and host genetics, may provide new insights into the underlying mechanisms of pathobiology which may allow us to modulate disease onset, prognosis, and survival 9,10 .Metabolomic profiling may provide additional insight into the processes affected by specific bacteria or when the composition of the microbiota is altered 11 . It has been shown that the gut microbiota can have a significant effect on plasma metabolic profile, which can modulate host health 12 . Therefore, pairing metabolomics and microbiota analysis may yield important mechanistic insights. For example, trimethylamine N-oxide (TMAO) was identified as a risk factor for cardiovascular disease through a metaorganismal pathway involving the microbiota and diet 13 .Laboratory mice are often used to investigate both genetic and microbiota to understand the underlying mecha...

Candida Species (Volatile) Metabotyping through Advanced Comprehensive Two‐Dimensional Gas Chromatography

“…Genetic differences promote differential expressions of genes implicated in the biosynthesis of volatile metabolites, or even promote different metabolites concentrations [23,24]. Metabolomic profiling may provide additional information about the processes affected by specific microorganisms or microbiota alterations or about the environment affects the organisms that are susceptible to environmental changes and stress conditions [24,25].…”

High poly-γ-glutamic acid-containing natto improves lipid metabolism and alters intestinal microbiota in mice fed a high-fat diet

“…Tsumura Suzuki Obese Diabetes (TSOD) mice show typical type 2 diabetes symptoms, and the abundance of Turicibacter is significantly greater in obese mice than in non-obese TSNO mice, ( 25 ) suggesting the importance of Turicibacter in the abnormal metabolism that occurs in type 2 diabetes. It has been reported that the relative abundances of Clostridiaceae , ( 26 ) Streptococcaceae , and Desulfovibrionaceae are positively associated with plasma glucose levels in mice. ( 27 ) In our results, the relative abundance of these bacterial families was positively correlated with plasma glucose levels.…”

The serum metabolic profile plays a role in mediating the regulatory impact of gut microbiota and its metabolites on susceptibility to obesity in mice

“…Variations in obesity-related genes, including but not limited to FTO, apolipoprotein A- (Wang et al, 2023), NR3C2, APOA4, hypothalamic LIF (Fioravante et al, 2017), and metabolic proteins in brown fat (Surwit et al, 1998) (Chang et al, 1990), play a crucial role in determining susceptibility to obesity. Several studies have suggested that certain serum metabolites may contribute to obesity susceptibility (Wei et al, 2020), with glycine, isoleucine, phenylalanine, phosphatidylcholine, phosphatidylethanolamine, and saturated fatty acids among those identi ed as having signi cant effects on body weight and fat mass (Pang et al, 2022) (Nazmul Huda et al, 2020). Numerous experiments have been conducted to address obesity through manipulation of serum metabolite levels, resulting in signi cant outcomes that underscore the pivotal role of serum metabolites in obesity susceptibility.…”