EVOLUTION: Of Mice . . .

Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease

Microbiome and type 1 diabetes.

Genetic Pathways in Nonalcoholic Fatty Liver Disease: Insights From Systems Biology.

Anti-inflammatory activity of alkali-soluble polysaccharides from Arctium lappa L. and its effect on gut microbiota of mice with inflammation

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut-liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9C58A0E320AB35547FE219EDF19F9AE6/S0029665118002756a.pdf/div-class-title-contribution-of-the-gut-microbiota-to-the-regulation-of-host-metabolism-and-energy-balance-a-focus-on-the-gut-liver-axis-div.pdf

Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis.

Purpose of reviewNonalcoholic fatty liver disease (NAFLD) is becoming the most important cause of chronic liver disease in Western countries but no pharmacological therapy is currently available. Growing evidence suggests that the microbiota plays a role in the occurrence and evolution of this disea

Microbiota and nonalcoholic fatty liver disease: promising prospects for clinical interventions?

BACKGROUND The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior. OBJECTIVES The aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD. METHODS Eight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4-5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5 mM, n ≥6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed. RESULTS Indole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motif chemokine ligand 2 (Cxcl2); 3.3- compared with 5.0-fold, and 2.4- compared with 3.3-fold of control ob/+ mice, respectively, P < 0.05], and in macrophage activation [Cd68, integrin subunit α X (Itgax); 2.1- compared with 2.5-fold, and 5.0- compared with 6.4-fold of control ob/+ mice, respectively, P < 0.01] as well as markers of hepatic damage (alaninine aminotransferase; -32%, P < 0.001) regardless of genotype in experiment 1. Indole had no effect on hepatic inflammation in mice fed the LF or HF diet in experiment 2. Indole did not change hepatic lipid content, anxiety-like behavior, or inflammation in the ileum, adipose tissue, and brain in experiment 1. CONCLUSIONS Our results support the efficacy of indole to reduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier.

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Christelle Knudsen

Papers

Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis.

Microbiota and nonalcoholic fatty liver disease: promising prospects for clinical interventions?

Hepatoprotective Effects of Indole, a Gut Microbial Metabolite, in Leptin-Deficient Obese Mice