Table 1_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.xlsx

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.

引言：特定抗反转录病毒治疗（antiretroviral therapy, ART）方案与人类免疫缺陷病毒感染者（people living with HIV, PLWH）的体重增加存在关联。肠道菌群（gut microbiota）在人类与动物的体重调控过程中发挥重要作用。人类肠道菌群可依据其独特的微生物组成与功能特征，划分为不同的肠型（enterotype）。
研究方法：本研究纳入118名HIV感染者队列，采用16S rRNA基因测序技术，结合肠型分类策略，分析肠道菌群与体重增加、抗反转录病毒治疗方案之间的关联。
研究结果：研究显示，肠型与性取向存在显著关联。在主坐标分析中，67名属于普氏菌（Prevotella）主导型肠型簇的个体中，93%为男男性行为者（men who had sex with men, MSM）；而在拟杆菌（Bacteroides）主导型肠型簇中，31%为男男性行为者，69%为非男男性行为者。男男性行为者与非男男性行为者之间共有49个菌属存在显著差异。按优势菌属分层分析后，仅6个分类单元与体重增加相关，其中5个仅存在于拟杆菌主导型个体中。在这些分类单元中，放线菌纲（Actinobacteria）和双歧杆菌属（Bifidobacterium）在抗反转录病毒治疗换药1年后，体重增加超过5%与体重增加不足5%的个体间存在显著差异。此外，在抗反转录病毒治疗换药1年后，体重增加最高的15%个体（体重增幅≥6.3%）与体重下降最高的个体（体重降幅≤3.19%）之间，共有3个分类单元存在显著差异，包括厚壁菌门（Firmicutes）、疣微菌门（Verrucomicrobia）和互养菌门（Synergistetes）。研究还观察到，仅在拟杆菌主导型肠型个体中，存在与体重增加相关的独特菌群功能特征，尤其体现在糖类与脂质代谢通路方面。此外，放线菌门的丰度存在抗反转录病毒治疗方案相关差异，但该差异仅见于普氏菌主导型肠型个体。
讨论：与体重增加和抗反转录病毒治疗方案相关的肠道菌群组成及功能特征差异具有肠型特异性，且相较于与性取向相关的菌群差异，上述差异相对较小。鉴于多数男男性行为者的肠道菌群结构存在显著差异，按肠型分类有助于识别与体重增加或抗反转录病毒治疗等变量相关的菌群组成差异——此类差异可能仅局限于某一特定肠型。该发现可进一步推动在肠型背景下，对参与体重增加或改变肠道菌群组成的微生物的鉴定工作。