Dolo Oumar, Coulibaly Fousseini, Somboro Anou M, Sun Shan, Diarra Modibo, Maiga Aminata, Bore Soungou, Fofana Djeneba B, Marcelin Anne-Genevieve, Diakite Brehima, Kassogue Yaya, Holl Jane L, Calvez Vincent, Traoré Cheick B, Murphy Robert, Fodor Anthony A, Maiga Mamoudou, Maiga Almoustapha I
University Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, Mali.
Medical Biology Laboratory of the Point G University Hospital Center, Bamako, Bamako Capital District, Mali.
Microbiol Spectr. 2025 Aug 5;13(8):e0220524. doi: 10.1128/spectrum.02205-24. Epub 2025 Jun 16.
The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to 6 and 12 months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants' intestinal microbial structures and derived metabolic pathways. Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in at 6 months of ART, continuing until 12 months of ART. Lower proportions of were noted pre-ART, but they increased slightly at 6 months of ART before decreasing again at 12 months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after 12 months of ART, and this mechanism was correlated with a decrease in species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.IMPORTANCEResearchers are facing a major challenge in the treatment of HIV infection due to the continuous use of antiretroviral (ARV) molecules. However, regularly monitoring these molecules is necessary because they are not without consequences. They have toxicity and side effects and could also destabilize the intestinal microbiota, which could harm the metabolic pathways essential to good health. This study reveals that ARV treatment only partially restores gut microbiota dysbiosis and alters metabolic pathways due to pathogenic taxa. This provides additional insights into the relationship between antiretroviral therapy and the microbiome, potentially leading to new prevention and treatment strategies such as probiotic/prebiotic or microbiota transplants.
人类肠道微生物群由高度复杂的微生物群体组成，这些群体在疾病发病机制中发挥着重要作用。肠道微生物群的变化与HIV感染有关。然而，目前尚不清楚肠道微生物群失调是否与疾病存在因果关系，或者它是否仅仅反映了疾病引起的宿主免疫和代谢系统的变化。本研究旨在描述和比较接受抗逆转录病毒治疗（ART）前、ART开始后6个月和12个月的HIV感染者（PL-HIV）与HIV阴性个体的肠道微生物组成及其衍生的代谢途径。采用全基因组微生物群测序结合生物信息学分析来表征参与者的肠道微生物结构及其衍生的代谢途径。与HIV阴性人群相比，PL-HIV在ART前后的肠道微生物群特征显示出明显的失调。促炎微生物的富集是PL-HIV在ART前失调的标志，在ART 6个月时有所下降，并持续至ART 12个月。在ART前观察到较低比例，但在ART 6个月时略有增加，随后在ART 12个月时再次下降。此外，我们报告了对健康特别重要且与ART前后失调相关的代谢变化。丙酮酸发酵为异丁醇代谢途径的改变在PL-HIV接受ART 12个月后仍然存在，并且这种机制与物种的减少相关。ART的开始似乎导致了几个关键代谢途径的变化，并且可能无法完全恢复由HIV引起的肠道微生物群失调。
重要性
由于抗逆转录病毒（ARV）分子被持续使用，研究人员在HIV感染治疗上面临重大挑战。然而，定期监测这些分子是必要的，因为它们并非没有后果。它们具有毒性和副作用，还可能破坏肠道微生物群，这可能损害对健康至关重要的代谢途径。本研究表明，ARV治疗仅部分恢复肠道微生物群失调，并因致病类群而改变代谢途径。这为抗逆转录病毒治疗与微生物群之间的关系提供了更多见解，可能会带来新的预防和治疗策略，如益生菌/益生元或微生物群移植。
