AUTHOR=Kehrmann Jan , Dostmohammadi Alireza , Stumpf Anna-Lena , Best Lara , Consten Leah , Sievert Hannah , Maischack Felix , Sammet Stefanie , Albayrak-Rena Sarah , Doerr Ann-Kathrin , Bohlen Katharina , von Velsen Otgonzul , Kraiselburd Ivana , Karsten Christina B. , Farahpour Farnoush , Meyer Folker , Esser Stefan , Buer Jan 

TITLE=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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1568352

DOI=10.3389/fcimb.2025.1568352

ISSN=2235-2988

ABSTRACT=IntroductionSpecific antiretroviral therapy (ART) regimens are associated with weight gain in people living with HIV (PLWH). Gut microbiota is involved in weight gain in humans and animals. Human gut microbiota can be classified into enterotypes with distinct microbial and functional profiles.MethodsIn 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.ResultsThe 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 had sex with men (MSM), while 31% of individuals in the Bacteroides-dominated enterotype cluster were MSM and 69% were non-MSM. Forty-nine genera differed significantly between the MSM and non-MSM individuals. When stratified by dominant genus, only six taxa were associated with weight gain. Of these, five were restricted to Bacteroides-dominated individuals. Among them, the class Actinobacteria and 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% of 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.DiscussionDifferences in the composition and functional characteristics of the gut microbiome associated with weight gain and ART regimens were enterotype-specific and relatively small compared with 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, which may be limited to a single enterotype. This may further advance the identification of microbes that contribute to weight gain or alter the gut microbiome composition in the context of the enterotype.