The gut microbiota modulates host energy and lipid metabolism in mice

Velagapudi, Vidya; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Borén, Jan; Orešič, Matej; Bäckhed, Fredrik

doi:10.1194/jlr.m002774

Cited by 519 publications

(404 citation statements)

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“…Probiotics and obesity in children R Luoto et al and fat deposition regulation. 11,36 Moreover, a high-fat diet increases the intestinal gram-negative to gram-positive bacterial ratio and thus the plasma lipopolysaccharide concentration, which sets the tone for metabolic endotoxemia and thus triggers the low-grade inflammatory state affecting insulin sensitivity. 12,13 Selective augmentation of Bifidobacterium species by prebiotic supplementation conversely, has been shown to be associated with improved glucose tolerance and decreased endotoxemia.…”

Section: Discussionmentioning

confidence: 99%

The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years

et al. 2010

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Background: The achievements in combating the increasing trend of overweight and obesity have thus far been inadequate. The recently discovered instrumental role of the gut microbiota in host metabolism may offer a novel target in the prevention and management of obesity. Objective: To evaluate the impact of perinatal probiotic intervention on childhood growth patterns and the development of overweight during a 10-year follow-up. Patients and methods: Altogether 159 women were randomized and double-blinded to receive probiotics (1 Â 10 10 colonyforming units of Lactobacillus rhamnosus GG, ATCC 53103) or placebo 4 weeks before expected delivery; the intervention extending for 6 months postnatally. Anthropometric measurements of the children were taken at the ages of 3, 6, 12 and 24 months and at 4, 7 and 10 years in 113 (72%) children. Results: The excessive weight gain was detected to be two-parted; the initial phase of excessive weight gain initiating during fetal period and continuing until 24-48 months of age and a second phase of excessive weight gain starting after the age of 24-48 months. The perinatal probiotic intervention appeared to moderate the initial phase of excessive weight gain, especially among children who later became overweight, but not the second phase of excessive weight gain, the impact being most pronounced at the age of 4 years (P ¼ 0.063, analysis of variance for repeated measures). The effect of intervention was also shown as a tendency to reduce the birth-weight-adjusted mean body mass index at the age of 4 years (P ¼ 0.080, analysis of covariance). Conclusions: Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life. This novel observation calls for further epidemiological and clinical trials, with precise data on early growth patterns and on confounding factors influencing weight development.

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Section: Discussionmentioning

confidence: 99%

The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years

et al. 2010

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“…Supporting this hypothesis, consistently higher tryptophan levels in urine were reported during the establishment of a gut microbiota compared with germfree animals 36 though another study reported lower serum tryptophan levels in conventional mice compared to germfree mice. 37 Interestingly, ex-germfree mice also displayed higher levels of phenylalanine, tyrosine, and tryptophan in the cerebral metabolome compared with germfree mice. 38 There is evidence that the gut microbiota influences the brain and behavior by regulating tryptophan availability as well as by synthesising and degrading tryptophan.…”

Section: Discussionmentioning

confidence: 99%

“…Consistently, conventional mice were reported to exhibit a greater than 1.5-fold increase in dopamine levels in serum compared to germfree mice. 37 Importantly, we predicted that all of the hormones and hormone precursors could be produced by the "germfree" host, but their secretion levels were drastically increased in the presence of the 11 microbes. These predictions are supported by experimental observations that germfree animals have a functional hormonal repertoire but exhibit an altered behavior, likely because of the lack of microbial influence on their hormone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework

2015

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Keywords: human gut microbiome, in silico, metabolome, metabolic modelingThe gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates "germfree" and "exgermfree" human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial cometabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism.

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“…Whereas the oral components are unlikely to directly contribute to cholesterol metabolism, they may serve as biomarkers. In contrast, the gut microbiota may directly affect host lipid metabolism (40). Although the exact mechanism remains to be identified, the gut microbiota is essential for bioconversion of cholesterol to bile acids, which are required for cholesterol excretion, as well as cholesterol absorption (41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Human oral, gut, and plaque microbiota in patients with atherosclerosis

Koren

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Felin

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis.

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The gut microbiota modulates host energy and lipid metabolism in mice

Cited by 519 publications

References 48 publications

The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years

The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years

Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework

Human oral, gut, and plaque microbiota in patients with atherosclerosis

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