From gut microbiota to brain: implications on binge eating disorders.

The prevalence of eating disorders has been increasing over the last 50 years. Binge eating disorder (BED) and bulimia nervosa (BN) are two typical disabling, costly and life-threatening eating disorders that substantially compromise the physical well-being of individuals while undermining their psychological functioning. The distressing and recurrent episodes of binge eating are commonly observed in both BED and BN; however, they diverge as BN often involves the adoption of inappropriate compensatory behaviors aimed at averting weight gain. Normal eating behavior is coordinated by a well-regulated trade-off between intestinal and central ingestive mechanism. Conversely, despite the fact that the etiology of BED and BN remains incompletely resolved, emerging evidence corroborates the notion that dysbiosis of gastrointestinal microbiome and its metabolites, alteration of gut-brain axis, as well as malfunctioning central circuitry regulating motivation, execution and reward all contribute to the pathology of binge eating. In this review, we aim to outline the current state of knowledge pertaining to the potential mechanisms through which each component of the gut-brain axis participates in binge eating behaviors, and provide insight for the development of microbiome-based therapeutic interventions that hold promise in ameliorating patients afflicted with binge eating disorders.

NLRP6 Inflammasome Modulates Disease Progression in a Chronic-Plus-Binge Mouse Model of Alcoholic Liver Disease.

A considerable percentage of the population is affected by alcoholic liver disease (ALD). It is characterized by inflammatory signals from the liver and other organs, such as the intestine. The NLR family pyrin domain containing 6 (NLRP6) inflammasome complex is one of the most important inflammatory mediators. The aim of this study was to evaluate a novel mouse model for ALD characterized by 8-week chronic-plus-binge ethanol administration and to investigate the role of NLRP6 inflammasome for intestinal homeostasis and ALD progression using Nlrp6-/- mice. We showed that chronic-plus-binge ethanol administration triggers hepatic steatosis, injury, and neutrophil infiltration. Furthermore, we discovered significant changes of intestinal microbial communities, including increased relative abundances of bacteria within the phyla Bacteroidota and Campilobacterota, as well as reduced Firmicutes. In this ALD model, inhibiting NLRP6 signaling had no effect on liver steatosis or damage, but had a minor impact on intestinal homeostasis via affecting intestinal epithelium function and gut microbiota. Surprisingly, Nlrp6 loss resulted in significantly decreased hepatic immune cell infiltration. As a result, our novel mouse model encompasses several aspects of human ALD, such as intestinal dysbiosis. Interfering with NLRP6 inflammasome activity reduced hepatic immune cell recruitment, indicating a disease-aggravating role of NLRP6 during ALD.

Specific gut microbial, biological, and psychiatric profiling related to binge eating disorders: A cross-sectional study in obese patients.

BACKGROUND & AIMS: Binge eating disorder (BED) is a frequent eating disorder associated with obesity and co-morbidities including psychiatric pathologies, which represent a big health burden on the society. The biological processes related to BED remain unknown. Based on psychological testing, anthropometry, clinical biology, gut microbiota analysis and metabolomic assessment, we aimed to examine the complex biological and psychiatric profile of obese patients with and without BED. METHODS: Psychological and biological characteristics (anthropometry, plasma biology, gut microbiota, blood pressure) of 101 obese subjects from the Food4Gut cohort were analysed to decipher the differences between BED and Non BED patients, classified based on the Questionnaire for Eating Disorder Diagnosis (Q-EDD). Microbial 16S rDNA sequencing and plasma non-targeted metabolomics (liquid chromatography-mass spectrometry) were performed in a subcohort of 91 and 39 patients respectively. RESULTS: BED subjects exhibited an impaired affect balance, deficits in inhibition and self-regulation together with marked alterations of eating behaviour (increased emotional and external eating). BED subjects displayed a lower blood pressure and hip circumference. A decrease in Akkermansia and Intestimonas as well as an increase in Bifidobacterium and Anaerostipes characterized BED subjects. Interestingly, metabolomics analysis revealed that BED subjects displayed a higher level of one food contaminants, Bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE.2H(2)O) and a food derived-metabolite the Isovalerylcarnitine. CONCLUSIONS: Non-targeted omics approaches allow to select specific microbial genera and two plasma metabolites that characterize BED obese patients. Further studies are needed to confirm their potential role as drivers or biomarkers of binge eating disorder. Food4gut, clinicaltrial.gov:NCT03852069, https://clinicaltrials.gov/ct2/show/NCT03852069.

A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders.

BACKGROUND: There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs. METHODS: This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs. RESULTS: Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation. CONCLUSIONS: Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut-brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders.

OBJECTIVE: Caseinolytic protease B (ClpB) produced by Enterobacteria, such as Escherichia coli, has been identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α-MSH cross-reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti-ClpB and anti-α-MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. METHODS: Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge-eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory-2 (EDI-2) scale. RESULTS: We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patient's subgroups. Plasma ClpB concentrations correlated with the EDI-2 scores, with α-MSH as well as with plasma levels of anti-ClpB and anti-α-MSH antibodies. DISCUSSION: These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED-related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805-808).