Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia

Shenoy, Meera K.; Iwai, Shoko; Lin, David L.; Worodria, William; Ayakaka, Irene; Byanyima, Patrick; Kaswabuli, Sylvia; Fong, Serena; Stone, Stephen; Chang, Emily; Davis, J. Lucian; Faruqi, Ali A.; Segal, Mark R.; Huang, Laurence; Lynch, Susan V.

doi:10.1164/rccm.201603-0523oc

Cited by 65 publications

(70 citation statements)

References 40 publications

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“…Lower airway microbial metagenomic functional capacity correlates with circulating metabolites and mortality in HIV-infected patients with pneumonia (Shenoy et al, 2016), providing evidence that active microbial metabolism affects the outcome of immune-compromised host. Paradoxically, genes encoding metabolic pathways for both propionate and butyrate were decreased in subjects with detectable propionate and butyrate.…”

Section: Discussionmentioning

confidence: 99%

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

Segal

Clemente

et al. 2017

Cell Host & Microbe

122

105

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Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested if SCFAs contribute to poor TB control in a longitudinal cohort of ART treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility. SCFAs inhibited IFN-γ and IL-17A production in peripheral blood mononuclear cells from HIV-infected ART-treated individuals in response to M. tuberculosis antigen stimulation. Pulmonary SCFAs correlated with increased oral anaerobes such as Prevotella in the lung and with M tuberculosis antigen-induced Tregs. Metabolites from anaerobic bacterial fermentation may therefore increase TB susceptibility by suppressing IFN-γ and IL-17A production during the cellular immune response to M. tuberculosis.

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Section: Discussionmentioning

confidence: 99%

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

Segal

Clemente

et al. 2017

Cell Host & Microbe

122

105

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“…The study also noted that specific metabolic features, including products of vitamin E, fatty acid, and arginine metabolism, were related to peripheral CD4 1 cell counts (28). More recently, using a cohort of 182 HIV-infected patients with pneumonia, Shenoy and colleagues demonstrated the existence of three compositionally distinct airway bacterial microbiota, each predicted to encode metagenomes capable of producing the metabolites detected in paired serum samples from these microbiologically stratified patient groups (29). Each pathogenic microbiota state induced a specific host immune response.…”

Section: Mechanisms Of Host Response and Diseasementioning

confidence: 94%

The Lung Microbiome and Airway Disease

Lynch

2016

Annals ATS

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A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

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“…This was demonstrated in a study of lean and obese individuals who were better differentiated by their gut metagenome as opposed to their microbiota profile . Finally, recent biomarker sequencing studies of large patient cohorts have demonstrated that several distinct microbiota conformations are evident in patients with a given clinical indication and are related to differences in immunologic profiles and clinical features of disease . This implies that within a given diseased patient population several pathogenic microbiomes may exist; however, such possibilities remain unexplored in the field of NAFLD microbiome research.…”

Section: The Gut Microbiome In Nafldmentioning

confidence: 99%

Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease

et al. 2018

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The gut microbiome, the multispecies community of microbes that exists in the gastrointestinal tract, encodes several orders of magnitude more functional genes than the human genome. It also plays a pivotal role in human health, in part due to metabolism of environmental, dietary, and host‐derived substrates, which produce bioactive metabolites. Perturbations to the composition and associated metabolic output of the gut microbiome have been associated with a number of chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). Here, we review the rapidly evolving suite of next‐generation techniques used for studying gut microbiome composition, functional gene content, and bioactive products and discuss relationships with the pathogenesis of NAFLD.

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Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia

Abstract: These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality.

Cited by 65 publications

References 40 publications

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

The Lung Microbiome and Airway Disease

Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease

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