Reduced Independence in Daily Living Is Associated with the Gut Microbiome in People with HIV and HCV
Bryn C. Taylor,
Kelly C. Weldon,
Ronald J. Ellis,
Donald Franklin,
Daniel McDonald,
Gregory Humphrey,
MacKenzie Bryant,
Julia Toronczak,
Tara Schwartz,
Jennifer Iudicello,
Robert Heaton,
Igor Grant,
Sara Gianella,
Scott Letendre,
Austin Swafford,
Pieter C. Dorrestein,
Rob Knight
Affiliations
Bryn C. Taylor
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Kelly C. Weldon
Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA
Ronald J. Ellis
Department of Neurosciences, HIV Neurobehavioral Research Center, University of California San Diego, La Jolla, California, USA
Donald Franklin
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA
Daniel McDonald
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA
Gregory Humphrey
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA
MacKenzie Bryant
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA
Julia Toronczak
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA
Tara Schwartz
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA
Jennifer Iudicello
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA
Robert Heaton
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA
Igor Grant
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA
Sara Gianella
Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA
Scott Letendre
Department of Medicine, University of California San Diego, La Jolla, California, USA
Austin Swafford
Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
Pieter C. Dorrestein
Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA
Rob Knight
Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
ABSTRACT Alterations in the gut microbiome are associated with neurocognition and related disorders, including in the context of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. However, the connection between the gut microbiome and cognitive decline, gauged by increased dependence in instrumental activities of daily living (IADL), remains largely unexplored in the context of these diseases. Here we characterized the gut microbiome using 16S rRNA amplicon sequencing and untargeted metabolomics with liquid chromatography-mass spectrometry from 347 people with HIV, HIV and HCV, or neither, all of whom underwent a comprehensive neuropsychiatric assessment. We observed that IADL-dependent and -independent HIV-monoinfected (HIV-positive [HIV+]/HCV-negative [HCV−]) and coinfected (HIV+/HCV+) individuals have distinct gut microbiomes. Moreover, we found that dependent individuals with HIV or HIV and HCV were enriched in Bacteroides. These results may have implications for the characterization of cognitive decline, as well as the development of potential prevention and treatment strategies for individuals infected with HIV and/or HCV. Of particular interest is the possibility that dietary interventions that are known to modify the microbiome could be used to shift the microbiome toward more favorable states for preserving independence. IMPORTANCE The microbes in the gut and the chemicals they produce by metabolism have been linked to brain function. In earlier work, we showed that infection with two viruses, HIV and HCV, changed the gut microbes and metabolism in ways that were associated with a lifetime history of major depressive disorder. Here, we extend this analysis looking at a measurement of independence in daily living. We find that in individuals with HIV, whether or not they also have HCV, those who reported reduced independence were enriched in a genus of bacteria called Bacteroides. This result is interesting because Bacteroides is strongly associated with diets low in carbohydrates and high in animal protein, suggesting that diet changes may help preserve independent living in people living long-term with HIV (although clinical intervention trials would be needed in order to confirm this).
