Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in add...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/1891 |
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| author | Ronald J. Ellis Jennifer E. Iudicello Robert K. Heaton Stéphane Isnard John Lin Jean-Pierre Routy Sara Gianella Martin Hoenigl Rob Knight |
| author_facet | Ronald J. Ellis Jennifer E. Iudicello Robert K. Heaton Stéphane Isnard John Lin Jean-Pierre Routy Sara Gianella Martin Hoenigl Rob Knight |
| author_sort | Ronald J. Ellis |
| collection | DOAJ |
| description | People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; <i>p</i> = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; <i>p</i> = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; <i>p</i> = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (<i>p</i> = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; <i>p</i> = 0.0017), but not for PWoH individuals (r = −0.0227; <i>p</i> = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role. |
| first_indexed | 2024-03-10T06:09:04Z |
| format | Article |
| id | doaj.art-037977cccf794b8a803040412774cb29 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:09:04Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-037977cccf794b8a803040412774cb292023-11-22T20:17:37ZengMDPI AGViruses1999-49152021-09-011310189110.3390/v13101891Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIVRonald J. Ellis0Jennifer E. Iudicello1Robert K. Heaton2Stéphane Isnard3John Lin4Jean-Pierre Routy5Sara Gianella6Martin Hoenigl7Rob Knight8Departments of Neurosciences and Psychiatry, University of California, San Diego, CA 92093, USADepartment of Psychiatry, University of California, San Diego, CA 92093, USADepartment of Psychiatry, University of California, San Diego, CA 92093, USAResearch Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, CanadaDepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Pediatrics, University of California, San Diego, CA 92093, USAPeople with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; <i>p</i> = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; <i>p</i> = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; <i>p</i> = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (<i>p</i> = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; <i>p</i> = 0.0017), but not for PWoH individuals (r = −0.0227; <i>p</i> = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role.https://www.mdpi.com/1999-4915/13/10/1891HIVgut microbial diversitygut barrier dysfunctionmicrobial translocationoccludin |
| spellingShingle | Ronald J. Ellis Jennifer E. Iudicello Robert K. Heaton Stéphane Isnard John Lin Jean-Pierre Routy Sara Gianella Martin Hoenigl Rob Knight Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV Viruses HIV gut microbial diversity gut barrier dysfunction microbial translocation occludin |
| title | Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV |
| title_full | Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV |
| title_fullStr | Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV |
| title_full_unstemmed | Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV |
| title_short | Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV |
| title_sort | markers of gut barrier function and microbial translocation associate with lower gut microbial diversity in people with hiv |
| topic | HIV gut microbial diversity gut barrier dysfunction microbial translocation occludin |
| url | https://www.mdpi.com/1999-4915/13/10/1891 |
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