Biology subjects

Palmer, B. E.

Publications and source records attributed to Palmer, B. E..

3 recordsLinked to original sources

bioRxiv2026

Amoxicillin induces gut dysbiosis leading to long term suppression of type-17 immune tone in the lungs

T-helper (Th)-17 lymphocytes are central mediators of adaptive type 17 immunity. Decreased type-17 signaling increases severity of infections in humans and mice. However, detrimental effects of excessive type 17 responses in autoimmune and other inflammatory diseases highlight a need for type-17 immune calibration to support beneficial host defense requirements. Mechanisms of type 17 calibration are poorly understood. A gut-lung axis has been proposed to coordinate homeostatic protection and acute host defense. Factors that acutely alter the gut microbiome are heterogeneous and include acute intestinal infections, non-infectious colitis, and medical treatments such as antibiotics. How changes in the gut microbiome affect lung immune tone during homeostasis and acute pulmonary infections are also poorly understood. Prior studies have shown that antibiotics reduce expression of IL-17-mediated host defense in the gut. Since gut microbial homeostasis influences Th17 cell numbers in both the intestine and remote tissues, we postulated that antibiotic treatment would result in gut dysbiosis and weakened type-17 host defense in the lungs. We found that amoxicillin induces significant dysbiosis that is long-lasting and that there is a long-term decrease in type-17 tone in the lungs. We also found that in mice lacking the gut mucin, Muc2, Th17 cells increased in the lungs following inflammatory challenge. These findings suggest that antibiotic-induced dysbiosis can decrease lung immune defenses for long periods of time after cessation of antibiotic treatment.

immunology↗

bioRxiv2021

Systems analysis of gut microbiome influence on metabolic disease in HIV and high-risk populations

Poor metabolic health, characterized by insulin resistance and dyslipidemia, is higher in people living with HIV and has been linked with inflammation, anti-retroviral therapy (ART) drugs, and ART-associated lipodystrophy (LD). Metabolic disease is associated with gut microbiome composition outside the context of HIV but has not been deeply explored in HIV infection nor in high-risk men who have sex with men (HR-MSM), who have a highly altered gut microbiome composition. Furthermore, the contribution of increased bacterial translocation and associated systemic inflammation that has been described in HIV-positive and HR-MSM individuals has not been explored. We used a multi-omic approach to explore relationships between impaired metabolic health, defined using fasting blood markers, gut microbes, immune phenotypes and diet. Our cohort included ART-treated HIV positive MSM with and without LD, untreated HIV positive MSM, and HR-MSM. For HIV positive MSM on ART, we further explored associations with the plasma metabolome. We found that elevated plasma lipopolysaccharide binding protein (LBP) was the most important predictor of impaired metabolic health and network analysis showed that LBP formed a hub joining correlated microbial and immune predictors of metabolic disease. Taken together, our results suggest the role of inflammatory processes linked with bacterial translocation and interaction with the gut microbiome in metabolic disease among HIV positive and negative MSM. Importance StatementThe gut microbiome in people living with HIV (PLWH) is of interest as chronic infection often results in long term comorbidities. Metabolic disease is prevalent in PLWH even in well-controlled infection and has been linked with the gut microbiome in previous studies, but little attention has been given to PLWH. Furthermore, integrated analyses that consider gut microbiome together with diet, systemic immune activation, metabolites, and demographics have been lacking. In a systems-level analysis of predictors of metabolic disease in PLWH and men who are at high risk of acquiring HIV, we found that increased LBP, an inflammatory marker indicative of compromised intestinal barrier function, was associated with worse metabolic health. We also found impaired metabolic health associated with specific dietary components, gut microbes, and host and microbial metabolites. This work lays the framework for mechanistic studies aimed at targeting the microbiome to prevent or treat metabolic endotoxemia in HIV-infected individuals.

microbiology↗

bioRxiv2018

An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men

BackgroundGut microbiome characteristics associated with HIV infection are of intense research interest but a deep understanding has been challenged by confounding factors across studied populations. Notably, a Prevotella-rich microbiome described in HIV-infected populations is now understood to be common in men who have sex with men (MSM) regardless of HIV status, but driving factors and potential health implications are unknown.\n\nResultsHere we further define the MSM-associated gut microbiome and describe compositional differences between the fecal microbiomes of Prevotella-rich MSM and non-MSM that may underlie observed pro-inflammatory properties. Furthermore, we show relatively subtle gut microbiome changes in HIV infection in MSM and women that include an increase in potential pathogens that is ameliorated with antiretroviral therapy (ART). Lastly, using a longitudinal cohort, we describe microbiome changes that happen after ART initiation.\n\nConclusionsThis study provides an in-depth characterization of microbiome differences that occur in a US population infected with HIV and demonstrates the degree to which these differences may be driven by lifestyle factors, ART and HIV infection itself. Understanding microbiome compositions that occur with sexual behaviors that are high-risk for acquiring HIV and untreated and ART-treated HIV infection will guide the investigation of immune and metabolic functional implications to ultimately target the microbiome therapeutically.

microbiology↗