Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases.

Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.

Gut microbiota metabolizes tryptophan into indole, which can influence brain and behavior. Indeed, some oxidized derivatives of indole, formed in the liver, have neuroactive properties, and indole overproduction by the gut microbiota induces an anxio-depressive phenotype in rodents. The aim of this study was to investigate in humans whether there was a relationship between recurrent depressive symptoms and indole production by the gut microbiota. A case-control study was conducted in 45–65-year-old women, who were participants in the observational prospective NutriNet-Santé Study. Cases were defined as having two Center for Epidemiological Studies-Depression Scales (CES-D) scores ≥ 23 at a two-year interval (recurrent depressive symptoms, n = 87). Each case was matched with two controls (two CES-D <23; n = 174). Urinary excretion of 3-indoxylsulfate, the major final metabolite of indole, was used as a biomarker of indole production by the gut microbiota. Conditional logistic regression models for paired data showed a positive association between urinary 3-indoxylsulfate concentrations, grouped in tertiles, and recurrent depressive symptoms (odds ratio = 2.46, p for trend = 0.0264 in the final model adjusted for confounding factors). This association suggested that indole production by the gut microbiota may play a role in the onset of mood disorders in humans.

In poultry, the selection of broilers for growth performance has induced a deterioration in the health of the parental hens associated with poor reproductive efficiency. To improve these parameters, we administered to laying parental broiler hens a regular diet supplemented or not (Control) with a moderate (1%) or a high level (2%) of grape seed extract (GSE). The 1% GSE diet was administered from a young age (from 4 to 40 weeks of age) and the high level of 2% GSE was administered only during a 2-week period (from 38 to 40 weeks of age) in the laying period. The analysis of 40-week-old hens showed that 2% GSE displayed a reduction in the fat tissue and an improvement in fertility with heavier and more resistant eggs. Seven monomer phenolic metabolites of GSE were significantly measured in the plasma of the 2% GSE hens. GSE supplementation increased the relative abundance of the following bacteria populations: Bifidobacteriaceae, Lactobacilliaceae and Lachnospiraceae. In conclusion, a supplementation period of only 2 weeks with 2% GSE is sufficient to improve the metabolic and laying parameters of breeder hens through a modification in the microbiota.

It has now been well established that gut microbiota significantly influences emotional and neuroendocrine responses to stress. Specifically, multiple pieces of evidence from various preclinical models indicate that gut microbiota regulates the response of the hypothalamic–pituitary‐adrenocortical (HPA) axis to acute and chronic stress. In contrast, the influence of gut microbiota on the adrenomedullary tissue, which is responsible for the production and release of catecholamines—the first hormones released in response to stress—has received little attention. Therefore, our study aimed to explore whether adrenal corticosterone and catecholamine biosynthesis were differently regulated in germ‐free (GF) and conventional, specific pathogen‐free (SPF) male rats when exposed to unpredictable chronic mild stress, acute metabolic stress, or both. Results showed that both GF and SPF chronically stressed rats had significantly ( p < 0.05) heavier adrenal glands (+30% for GF, +21% for SPF) compared to unstressed animals. Gene expression levels of corticosterone biosynthesis enzymes and plasma and adrenal corticosterone concentrations did not differ significantly between control rats and those exposed to chronic, acute, or both stress factors, whether in GF or SPF rats. The same result was observed for the genes encoding tyrosine hydroxylase and dopamine β‐hydroxylase, two enzymes involved in catecholamine biosynthesis. By contrast, GF rats exhibited a 2.3‐fold increase ( p = 0.0271) in Pnmt gene expression (which encodes phenylethanolamine N‐methyltransferase, the enzyme responsible for converting norepinephrine to epinephrine) and a 2.6‐fold increase ( p = 0.0786) in epinephrine concentration in the adrenal glands under combined stress conditions. This response was not observed in SPF rats. In these animals, chronic stress was found to reshape the composition and metabolic functions of the gut microbiota. Interestingly, this was accompanied by a 40% decrease in norepinephrine ( p = 0.0364) and epinephrine ( p = 0.0840) concentrations in their adrenal glands. This study highlights the gut microbiota as a regulator of adrenomedullary activity, enhancing our understanding of the interaction between peripheral and central stress circuitry. image