Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests

Abstract

Anorexia nervosa (AN) is a psychiatric disease with devastating physical consequences, with a pathophysiological mechanism still to be elucidated. Metagenomic studies on anorexia nervosa have revealed profound gut microbiome perturbations as a possible environmental factor involved in the disease. In this study we performed a comprehensive analysis integrating data on gut microbiota with clinical, anthropometric and psychological traits to gain new insight in the pathophysiology of AN. Fifteen AN women were compared with fifteen age-, sex- and ethnicity-matched healthy controls. AN diet was characterized by a significant lower energy intake, but macronutrient analysis highlighted a restriction only in fats and carbohydrates consumption. Next generation sequencing showed that AN intestinal microbiota was significantly affected at every taxonomic level, showing a significant increase of Enterobacteriaceae, and of the archeon Methanobrevibacter smithii compared with healthy controls. On the contrary, the genera Roseburia, Ruminococcus and Clostridium, were depleted, in line with the observed reduction in AN of total short chain fatty acids, butyrate, and propionate. Butyrate concentrations inversely correlated with anxiety levels, whereas propionate directly correlated with insulin levels and with the relative abundance of Roseburia inulinivorans, a known propionate producer. BMI represented the best predictive value for gut dysbiosis and metabolic alterations, showing a negative correlation with Bacteroides uniformis (microbiota), with alanine aminotransferase (liver function), and with psychopathological scores (obsession-compulsion, anxiety, and depression), and a positive correlation with white blood cells count. In conclusion, our findings corroborate the hypothesis that the gut dysbiosis could take part in the AN neurobiology, in particular in sustaining the persistence of alterations that eventually result in relapses after renourishment and psychological therapy, but causality still needs to be proven.

Gut Microbiota Changes in Patients with Bipolar Depression

“…[28] An animal study showed that increased abundance in Clostridium was related to antidepressant-like effects in susceptible mice. Among BD patients, BMI was positively associated with Roseburia abundance, but negatively correlated with Clostridium IV, Dorea, Holdemania, Veillonella, Phascolarctobacterium, Eggerthella, Oscillibacter, Bilophila, Flavonifractor, Solobacterium, and Corynebacterium.…”

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia‐Induced Malnutrition in Mice

“…Interestingly, autophagy also plays a key role in the gut barrier function while gut microbiota is altered during chronic food restriction associated to a persistent weight loss . During anorexia‐induced body weight loss, gut microbiota is modified both in animals and in humans . Armougom et al .…”

“…It is well established that AN patients exhibit altered microbiota, as also observed during the ABA model . Microbiota–gut–brain axis occurs in the regulation of feeding but also in the occurrence of anxiety or depression, comorbidities frequently observed in AN patients. Stress is another major factor in AN pathophysiology.…”

“…Recently, by using the activity‐based anorexia (ABA) model mimicking restrictive anorexia and long‐term body weight loss, we reported an increased colonic permeability associated with decreased colonic protein content and TLR4 activation leading to an inflammatory response . It is well established that AN patients exhibit altered microbiota, as also observed during the ABA model . Microbiota–gut–brain axis occurs in the regulation of feeding but also in the occurrence of anxiety or depression, comorbidities frequently observed in AN patients.…”

Reconceptualizing anorexia nervosa

“…A possible explanation for the discrepancies between these two findings could be differences in the lifestyle and diet in Japanese versus European participants. In two more recent publications, AN patients were reported to have reduced excretion of fecal butyrate and propionate compared to healthy individuals . In addition, the concentrations of butyrate were inversely correlated with levels of anxiety in patients with AN …”