Gut microbiota differences linked to weight gain and ART in people living with HIV are enterotype specific and minor compared to the large differences linked to sexual behavior

Jan Kehrmann ^1* Alireza Dostmohammadi ² Anna-Lena Stumpf ¹ Lara Best ¹ Leah Consten ¹ Hannah Sievert ¹ Felix Maischack ³ Stefanie Sammet ³ Sarah Albayrak-Rena ³ Ann-Kathrin Doerr ⁴ Katharina Bohlen ⁵ Otgonzul von Velsen ⁶ Ivana Kraiselburd ⁴ Christina B. Karsten ⁷ Farnoush Farahpour ^2,8 Folker Meyer ⁴ Stefan Esser ³ Jan Buer ¹

• ¹ Institute for Medical Microbiology, University Hospital Essen, Essen, Germany
• ² Department of Bioinformatics and Computational Biophysics, Faculty of Biology, University of Duisburg-Essen, Essen, North Rhine-Westphalia, Germany
• ³ Clinic for Dermatology, University Hospital of Essen, Essen, North Rhine-Westphalia, Germany
• ⁴ Institute for Artificial Intelligence in Medicine, University Hospital Essen, Essen, Germany
• ⁵ Department of Gastroenterology, Hepatology and Transplantational Medicine, University Hospital Essen, Essen, Germany
• ⁶ Institute for Medical Informatics, Biometry and Epidemiology, Essen University Hospital, Essen, North Rhine-Westphalia, Germany
• ⁷ Institute for the Research on HIV and AIDS-associated Diseases, University Hospital Essen, Essen, Germany
• ⁸ Institute of Cell Biology (Cancer Research), University Hospital Essen, Essen, North Rhine-Westphalia, Germany

Specific antiretroviral therapy (ART) regimens are associated with weight gain in people living with HIV (PLWH). The gut microbiota is involved in weight gain in humans and animals. The human gut microbiota can be classified into enterotypes with distinct microbial and functional profiles. In a cohort of 118 PLWH, we analyzed the gut microbiome in relation to weight gain and ART regimen using 16S rRNA gene sequencing, taking enterotype classification into account. The enterotype was strongly associated with sexual orientation. Of the 67 individuals forming a Prevotella dominated enterotype cluster in principal coordinates analysis, 93% were men who have sex with men (MSM), while 31% of individuals of the Bacteroides dominated enterotype cluster were MSM and 69% were non-MSM. Forty-nine genera differed significantly between MSM and non-MSM individuals. When stratified by the dominating genus, only six taxa were associated with weight gain. Of these, five were restricted to Bacteroides dominated individuals. Among them, the class Actinobacteria and the genus Bifidobacterium differed between individuals gaining more than 5% weight and less than 5% weight 1 year after ART switch. Additionally, three taxa were significantly different between 15% individuals with the highest weight gain (≥6.3%) and the highest weight loss (≤3.19%) 1 year after ART switch including the phyla Firmicutes, Verrucomicrobia and Synergistetes. Distinct functional properties in Bacteroides but not Prevotella dominated enterotype individuals linked to weight gain were observed, particularly for glycan and lipid metabolism. Additionally, ART regimen-associated differences were observed for the phylum Actinobacteria, although this was limited to Prevotella dominated enterotype individuals. Differences in the composition and functional characteristics of the gut microbiome associated with weight gain and ART regimens were enterotype specific and relatively small compared to differences linked to sexual orientation. Due to the substantial differences in gut microbiome structure among many MSM, categorization into enterotypes is useful for identifying differences in microbiome composition associated with variables such as weight gain or ART that may be limited to a single enterotype. This may further advance the identification of microbes that contribute to weight gain or alter gut microbiome composition in the context of the enterotype.