Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice

Abstract

Anorexia nervosa (AN) is a psychiatric disorder that presents with profound weight dysregulation, metabolic disturbances, and an abnormal composition of gut microbial communities. As the intestinal microbiota can influence host metabolism, the impact of enteric microbial communities from patients with AN on host weight and adiposity was investigated. Germ-free (GF) mice were colonized with fecal microbiotas from either patients with AN (n = 4) prior to inpatient treatment (AN T1, n = 50 recipient mice), the same 4 patients following clinical renourishment (AN T2, n = 53 recipient mice), or age- and sex-matched non-AN controls (n = 4 human donors; non-AN, n = 50 recipient mice). Biological and fecal microbiota data were analyzed with linear mixed-effects models. Body weight did not differ significantly between AN recipient mice (T1 and T2) and non-AN recipient mice following 4 weeks of colonization. Enteric microbiotas from recipient mice colonized with AN T1 and AN T2 fecal microbiotas were more similar to each other compared with enteric microbiotas from non-AN recipient mice. Specific bacterial families in the Actinobacteria, Bacteroidetes, and Firmicutes phyla were significantly associated with body weight, fat mass, and cecum weight irrespective of the donor group. These data suggest that body weight, fat mass, and cecum weight of colonized GF mice are associated with human fecal microbes and independent of donor AN status, although additional analyses with larger cohorts are warranted.

Reproducible changes in the anorexia nervosa gut microbiota following inpatient therapy remain distinct from non-eating disorder controls

“…Although our study does not address causality, recent studies transplanting fecal samples from patients with AN and non-ED controls into GF mice have addressed this phenomenon with mixed results. 11 , 22 The data reported here complement these studies by identifying specific bacterial taxa that may have a causative influence on host adiposity. Specifically, Bifidobacterium adolescentis and Faecalibacterium prausnitzii , depleted in patients with AN, are potential candidates to be used in gnotobiotic studies (mono-/dual-association or a consortium of microbes) coupled with calorie restriction, refeeding, or precision nutrition experiments to examine the contribution of enteric microbes to intestinal dysfunction in the context of nutrient deprivation.…”

Reframing anorexia nervosa as a metabo-psychiatric disorder

“…The GF mice colonized with an AN microbiota exhibited decreased weight gain compared with mice colonized with non-AN control microbiotas. By contrast, Glenny et al [36] reported no differences in weight gain, fat or lean mass, or food consumption between GF mice colonized by gut microbiotas from AN patients and unaffected controls. Although both studies used a gnotobiotic (Greek; 'gnotos' meaning known and 'bios' meaning life) approach to address the same question, multiple technical differences could explain the diverging results.…”

“…Therefore, whether the changes in the intestinal microbiota found in patients with AN influence specific clinical hallmarks of the illness (i.e., weight dysregulation) or are merely a consequence of a nutrient-deprived environment warrants careful exploration. To date, most studies investigating the role of the gut microbiota in AN have compared gut microbial communities between patients with AN and unaffected controls [29][30][31][32][33][34]; however, only two studies have attempted to determine the influence of gut microbiotas from patients with AN on the host, with contrasting results [35,36].…”

Possible role of the gut microbiota in the pathogenesis of anorexia nervosa

“…Bacteria, such as Bacteroides vulgatus, may play a protective role against the development of pathologies specific to patients with AN. Recently, Glenny et al [ 59 ] reported that fecal transplantation from patients with AN exerted no significant effects on body weight in GF mice. A precise reason for this discrepant result is unclear; however, this may be related to the methodology of fecal transplantation, which involved the use of frozen feces, as they suggested.…”