Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: microbiome-related factors associated with clinical outcome.

There is mounting evidence regarding the role of gut microbiota in anorexia nervosa (AN). Previous studies have reported that patients with AN show dysbiosis compared to healthy controls (HCs); however, the underlying mechanisms are unclear, and data on influencing factors and longitudinal course of microbiome changes are scarce. Here, we present longitudinal data of 57 adolescent inpatients diagnosed with AN at up to nine time points (including a 1-year follow-up examination) and compare these to up to six time points in 34 HCs. 16S rRNA gene sequencing was used to investigate the microbiome composition of fecal samples, and data on food intake, weight change, hormonal recovery (leptin levels), and clinical outcomes were recorded. Differences in microbiome composition compared to HCs were greatest during acute starvation and in the low-weight group, while diminishing with weight gain and especially weight recovery at the 1-year follow-up. Illness duration and prior weight loss were strongly associated with microbiome composition at hospital admission, whereas microbial changes during treatment were associated with kilocalories consumed, weight gain, and hormonal recovery. The microbiome at admission was prognostic for hospital readmission, and a higher abundance of Sutterella was associated with a higher body weight at the 1-year follow-up. Identifying these clinically important factors further underlines the potential relevance of gut microbial changes and may help elucidate the underlying pathophysiology of gut-brain interactions in AN. The characterization of prognostically relevant taxa could be useful to stratify patients at admission and to potentially identify candidate taxa for future supplementation studies aimed at improving AN treatment.

Undiagnosed uterine anomalies revealed by breech on ultrasound prior to external cephalic version - A chance to take a closer look.

OBJECTIVE: Uterine anomalies (UA) occur in up to 6.7% of women. Breech is eight times more likely to occur with UA which may not be diagnosed prior to pregnancy and may only be found in the third trimester with breech. The objective of the study is to assess the prevalence of both already known and newly sonographically diagnosed UA in breech from 36 weeks of gestation and its impact on external cephalic version (ECV), delivery options and perinatal outcomes. STUDY DESIGN: We recruited 469 women with breech at 36 weeks of gestation over a 2-year period at the Charité University Hospital, Berlin. Ultrasound examination was performed to rule out UA. Patients with known and newly 'de novo' diagnosed anomalies were identified and delivery options and perinatal outcomes analyzed. RESULTS: The 'de novo' diagnosis of UA at 36-37 weeks of pregnancy with breech was found to be significantly higher compared to the diagnosis prior to pregnancy with 4.5% vs 1.5% (p < 0.001 and odds ratio 4 with 95% confidence interval 2.12-7.69). Anomalies found included 53.6% bicornis unicollis, 39.3% subseptus, 3.6% unicornis and 3.6% didelphys. A trial of vaginal breech delivery was successful in 55.5% of cases when attempted. There were no successful ECVs. CONCLUSION: Breech is a marker for uterine malformation. Diagnosis of UA with breech can be up to four times improved with focused ultrasound screening in pregnancy even from 36 weeks of gestation prior to ECV to identify missed anomalies. Timely diagnosis aids antenatal care and delivery planning. Importantly, definitive diagnosis and treatment can be planned postpartum to improve outcomes in future pregnancies. ECV plays a limited role in selected cases.

Neural mechanisms underlying social recognition and theory of mind in adolescent patients with bulimia nervosa and transdiagnostic comparison with anorexia nervosa.

INTRODUCTION: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking. METHODS: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]). RESULTS: Compared to HCBN , patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency. DISCUSSION: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.

Gut microbiota alteration in adolescent anorexia nervosa does not normalize with short-term weight restoration.

OBJECTIVE: Gut microbiota are linked to metabolic function, body weight regulation, and brain and behavioral changes. Alteration of gut microbiota is repeatedly demonstrated in adults with anorexia nervosa (AN) and transplantation of stool from adult patients with AN reduces weight gain, food consumption and food efficiency in germ-free mice. No similar data are available for adolescents, who might differ from adults due to their shorter duration of illness. METHOD: Nineteen female adolescent patients with AN at admission and after short-term weight recovery were included in a longitudinal study and compared to 20 healthy controls (HC). DNA was extracted from stool samples and subjected to 16S rRNA gene sequencing and analysis. Group comparisons, indicator genera and simper analysis were applied. Taxon abundances at admission was used to predict inpatient treatment duration. RESULTS: Alpha diversity is increased in patients with AN after short-term weight recovery, while beta diversity shows clear group differences with HC before and after weight gain. A reduction in Romboutsia and taxa belonging to Enterobacteriaceae at both timepoints and an increase in taxa belonging to Lachnospiraceae at discharge are most indicative of patients. Lachnospiraceae abundance at admission helped to predict shorter inpatient treatment duration. DISCUSSION: This pilot study provides first evidence of gut microbiota alterations in adolescent patients with AN that do not normalize with weight gain. If verified in larger studies, the predictive power of taxa belonging to Lachnospiraceae for clinical outcome could complement known predictors at admission, inform clinicians and serve as a target for nutritional interventions.