Urvinder Kaur, M.Sc.
Nominated From: University of Washington
Research Site: Jawaharlal Nehru University
Research Area: Oral microbiome and HIV pathogenesis
Primary Mentor: Ravi Tandon
To study the colonization of oral microbiota in the gut of HIV-infected subjects and its role in the disease progression
According to UNAIDS report 2018, there are approximately 36.9 million people living with HIV worldwide and 1.8 million people became newly infected. In the era of antiretroviral therapy (ART), the disease progression has been controlled and the life expectancy of HIV-infected individuals has substantially increased. However, with expanded life span, HIV-infected individuals have high prevalence of non-AIDS conditions such as cardiovascular disease, renal and hepatic disease, neurocognitive impairment, bone disorders and non-AIDS malignancies. HIV infection induces rapid and significant depletion of CD4+ Th17 cells in gut associated lymphoid tissues, disruption of gut epithelial barrier and translocation of microbes or microbial products from gut lumen to systemic circulation. HIV-induced damage to gut homeostasis has been reported to associate with gut bacterial dysbiosis, which is represented by decreased abundance of beneficial bacteria and increased abundance of pathogenic bacteria. Both microbial translocation and gut bacterial dysbiosis contributes to persistent immune activation and inflammation, which remains one of the major causes of non-AIDS morbidity and mortality among HIV-infected individuals despite therapy. Human gut microbiota plays very crucial role in the development and maintenance of host physiological processes. They help in digestion, prevent colonization of harmful pathogens, modulate immune system and maintain gut epithelial barrier integrity. Indeed, dysbiosis has been associated with numerous chronic inflammatory and metabolic diseases like inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), diabetes, obesity, rheumatoid arthritis, allergic disease, multiple sclerosis, periodontal disease as well as HIV infection. HIV-infected subjects had altered gut microbiota composition, regardless of ART. Alterations in gut microbiota were shown to associate with CD4 recovery in treated HIV-infected subjects. Though gut microbiota inhibit colonization of non-native bacteria and the expansion of opportunistic pathogens, increased abundance of bacteria of oral origin has been described in the gut microbiota of subjects with several diseases including HIV. Further, HIV-infected subjects reported to have gastric hypochlorhydria. In healthy individuals, gastric acid helps to inactivate or kill swallowed pathogens, however increased gastric pH in HIV-infected subjects might allow the oral pathogens to reach gut. Further, the strains of Klebsiella species from oral microbiota has been reported to colonize in the gut of specific germ free mice and induce intestinal immune system, leading to chronic inflammation. Based on this work, we hypothesized that the colonization of subset of oral microbiota in the dysbiotic gut of treated HIV-infected subjects could induce inflammatory immune responses. Thus we aimed to study the association of colonization of oral bacteria in the gut with immune recovery, microbial translocation, persistent systemic immune activation and inflammation in treated HIV-infected subjects.
This study will allow us to identify novel microbiota for the reversal of oral microbiota colonization in the gut that may be associated with the treatment failure and elevated inflammation in HIV-infected subjects on treatment. This study will also help to develop therapeutic interventions that could restore healthy gut microbiota, alleviate increased inflammation and prevent diabetes, cardiovascular disease or other associated complications in treated HIV-infected subjects.
- Dr. Ravi Tandon, Ph.D., Assistant Professor, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
- Dr. Lishomwa C. Ndhlovu, MD, Ph.D., Professor, Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawai‘i at Manoa.
- Dr. Nishant Dev, MD, Assistant Professor, Department of medicine, Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India.
- Dr. Sameer Gulati, MD, Associate Professor, Department of medicine, Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India