Gut Microbiome Alterations Accompany Metabolic Normalization Following Bariatric Surgery in ROHHAD Syndrome

Abstract

Rapid onset obesity with hypoventilation, hypothalamic, and autonomic dysregulation (ROHHAD) syndrome in childhood is characterized by abrupt onset weight gain and dysautonomia with variable neuroendocrine involvement. In the absence of definitive disease-modifying therapies, the primary management strategy remains symptom control. This case report describes the first successful correction of obesity, dysautonomia, and metabolic derangement in a patient with ROHHAD following Roux-en-Y gastric bypass. Anthropometrics, metabolic profiling, and stool microbiome composition were assessed in a longitudinal fashion. In the 48-month period following surgery, the patient body mass index (BMI) reduced by 9.5 kg/m² and metabolic status improved, evidenced in weaning of insulin, and improved glycated hemoglobin, lipid profile, and hepatic enzymes. Chronic diarrhea resolved after surgery and prior to significant weight loss. Evaluation of stool bacterial composition and biomass demonstrated shifts in absolute abundance and taxonomic composition in longitudinal samples following surgery. This case demonstrates the potential efficacy of bariatric surgery in correcting the metabolic disruption of ROHHAD syndrome, producing long-term changes in gut microbiome composition and biomass.

Keywords: ROHHAD; bariatric surgery; gastroenterology; microbiome; obesity.

Figure 1.

Changes in weight loss and gut microbiome composition and abundance following bariatric surgery in ROHHAD case. Change in BMI (A) and weight (B) from baseline over the course of treatment and follow-up from age 12 to 21 years. The date of Roux-en-Y gastric bypass is annotated by a broken vertical line. Relative abundances of ASVs that represent bacterial composition were identified by 16S rRNA gene sequencing from stool samples collected at baseline and after surgery (1 year and 3 years post-Roux-en-Y gastric bypass). (C) Bar plots show alpha-diversity measured by Chao-1 and Shannon indices. (D-E) Alluvial plots show relative abundances (D) or absolute abundances (E) of bacterial genera. Lines connecting the columns show identical bacterial genera present across adjacent stool samples. (D) Bacterial genera are grouped by phyla as indicated by color. (E) Stool bacterial biomass was quantified by flow cytometry and normalized by 1 g of dry stool. Alluvial plots show the absolute abundances of each bacterial genus. Bacterial genera are grouped by phyla as indicated by color. Abbreviations: ASV, amplicon sequence variant; BMI, body mass index; RYGB, Roux-en-Y gastric bypass.