Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV.
| العنوان: | Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV. |
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| المؤلفون: | Singh S; The Wistar Institute., Giron LB; The Wistar Institute., Shaikh MW; Rush University Medical Center., Shankaran S; Rush University., Engen PA; Rush University Medical Center., Bogin ZR; Rush University Medical Center., Bambi SA; Rush University Medical Center., Goldman AR; The Wistar Institute., Azevedo JLLC; The Wistar Institute., Orgaz L; Life Length (Spain)., de Pedro N; Life Length (Spain)., González P; Life Length (Spain)., Giera M; Leiden University Medical Center., Verhoeven A; Leiden University Medical Center., Sánchez-López E; Leiden University Medical Center., Pandrea IV; University of Pittsburgh., Kannan T; The Wistar Institute., Tanes CE; Children's Hospital of Philadelphia., Bittinger K; Children's Hospital of Philadelphia., Landay AL; Rush University., Corley MJ; Cornell University., Keshavarzian A; Rush University Medical Center., Abdel-Mohsen M; The Wistar Institute. |
| المصدر: | Research square [Res Sq] 2023 Oct 30. Date of Electronic Publication: 2023 Oct 30. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| مستخلص: | Background: People with HIV (PWH), even with controlled viral replication through antiretroviral therapy (ART), experience persistent inflammation. This is partly due to intestinal microbial dysbiosis and translocation. Such ongoing inflammation may lead to the development of non-AIDS-related aging-associated comorbidities. However, there remains uncertainty regarding whether HIV affects the biological age of the intestines and whether microbial dysbiosis and translocation influence the biological aging process in PWH on ART. To fill this knowledge gap, we utilized a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PWH on ART and their matched HIV-negative counterparts. Results: Despite having similar chronological ages, PWH on ART exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to HIV-negative controls. Investigating the relationship between microbial translocation and biological aging, PWH on ART had decreased levels of tight junction proteins in the colon and ileum, along with increased microbial translocation. This increased intestinal permeability correlated with faster intestinal and systemic biological aging, as well as increased systemic inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PWH on ART had higher abundance of specific pro-inflammatory bacterial genera, such as Catenibacterium and Prevotella . These bacteria significantly correlated with accelerated local and systemic biological aging. Conversely, the intestines of PWH on ART had lower abundance of bacterial genera known for producing short-chain fatty acids and exhibiting anti-inflammatory properties, such as Subdoligranulum and Erysipelotrichaceae , and these bacteria taxa were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbial-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid and oleic acid. Conclusions: We identified a specific microbial composition and microbiome-related metabolic pathways that are intertwined with both intestinal and systemic biological aging in PWH on ART. A deeper understanding of the mechanisms underlying these connections could potentially offer strategies to counteract premature aging and its associated health complications in PWH. Competing Interests: Competing interests The authors have no competing interests. |
| التعليقات: | Update in: Microbiome. 2024 Feb 22;12(1):31. (PMID: 38383483) |
| معلومات مُعتمدة: | R01 AA029859 United States AA NIAAA NIH HHS; R01 AG062383 United States AG NIA NIH HHS; R01 DK123733 United States DK NIDDK NIH HHS; S10 OD023586 United States OD NIH HHS; P30 CA010815 United States CA NCI NIH HHS; P30 AI045008 United States AI NIAID NIH HHS; R24 AA026801 United States AA NIAAA NIH HHS; R01 NS117458 United States NS NINDS NIH HHS; R21 AI170166 United States AI NIAID NIH HHS; R01 AI165079 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: HIV; aging clocks; biological aging; gut; intestines; metabolome; microbiome |
| تواريخ الأحداث: | Date Created: 20231114 Latest Revision: 20240304 |
| رمز التحديث: | 20240304 |
| مُعرف محوري في PubMed: | PMC10635386 |
| DOI: | 10.21203/rs.3.rs-3492242/v1 |
| PMID: | 37961645 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.21203/rs.3.rs-3492242/v1 |
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