Microbial Short Chain Fatty Acids Impair Mycobacterium Avium (MAC) Clearance by Alveolar Macrophages

Carpenito, J.; Wu, Benjamin; Sulaiman, I.; Kurz, Sebastian; Li, Y.; Pérez, Laura; Franca, Brendan; Olsen, Eric; Gonzalez, Alexis Perez; Yie, K.; Ma, Sud; Naidoo, C; Theron, Grant; Weiden, Michael D.; Basavaraj, Ashwin; Tsay, Jia-Fang; Condos, Rany; Kamelhar, David; Addrizzo-Harris, Doreen

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a4242

Cited by 2 publications

(9 citation statements)

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“…Particularly, butyrates reduced the phagocytic and mycobactericidal (including against nontuberculous mycobacteria) ability of macrophages, increased the production of IL‐10, and decreased H37Rv‐induced production of proinflammatory cytokines, such as TNF‐α, IL‐1β, and IL‐17, in a dose‐dependent manner, increasing the proliferation of mycobacteria in macrophages (Figs. and ; and Table ) …”

Section: Antimicrobials Microbiome Immunity and Mtbmentioning

confidence: 93%

“…2 and 3; and Table 1). 47,54 Yet, its effects on H37Rv-induced IL-6, IFN-γ, and IL-22 production were insignificant. Thus, these SCFAs are not beneficial to the immune system in terms of TB, but are beneficial to diabetes, as IL-10 reduces insulin resistance and obesity.…”

Section: Metabolites-immunitymentioning

confidence: 97%

“…38,46 These suggest that other pathologies, such as HIV, which negatively affects the immune system and autophagy, can indirectly affect Mtb through the microbiome. 17,47 Yang et al observed a significant alteration and reduced diversity in the microbiota of atg5 knockout mice such that inflammation-reducing species, such as Akkermansia muciniphila and members of the Lachnospiraceae family, diminished, while proinflammatory (Candidatus athromitus) and pathogenic (Pasteurellaceae) bacteria flourished ( Fig. 1).…”

Section: Immunity (Autophagy)-microbiome Interactionsmentioning

confidence: 99%

“…2 and 3). 17,47,55 In an earlier study, Winglee et al showed that pulmonary Mtb infections affected the gut microbiota in mice, albeit few or no Mtb cells were found in the gut. 9 The dysbiosis was thus shown to be more as a result of the immune response to the Mtb infection than to the presence of Mtb in the gut, indicating the close relationship between the immune system and the lung-gut microbiome.…”

Section: Mtb-microbiome Interactionsmentioning

confidence: 99%

“…Specifically, autophagy shapes the contents of the microbiome, which, in turn, also modulates immune responses . These suggest that other pathologies, such as HIV, which negatively affects the immune system and autophagy, can indirectly affect Mtb through the microbiome …”

Section: Antimicrobials Microbiome Immunity and Mtbmentioning

confidence: 99%

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Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Sekyere

Maningi

Fourie

2020

Annals of the New York Academy of Sciences

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Increasingly, gut microbiota distortions are being implicated in the pathogenesis of several infectious and noninfectious diseases. Specifically, in the absence of an eubiotic microbiota, mice are more prone to colonization and infection by Mycobacterium tuberculosis (Mtb). In this qualitative analysis, the following were observed: (1) antimicrobials cause long-term gut microbiota perturbations; (2) Mtb causes limited and transient disturbances to the lung-gut microbiota; (3) pathogens (e.g., Helicobacter hepaticus) affect microbiota integrity and reduce resistance to Mtb; (4) dysbiosis depletes bacterial species regulating proper immune functioning, reducing resistance to Mtb; (5) dysregulated immune cells fail to express important pathogen-recognition receptors (e.g., macrophageinducible C-type lectin; MINCLE) and Mtb-killing cytokines (e.g., IFN-γ, TNF-α, and IL-17), with hampered phagocytic capability; (6) autophagy is central to the immune system's clearance of Mtb, control of inflammation, and immunity-microbiome balance; (7) microbiota-produced short-chain fatty acids, which are reduced by dysbiosis, affect immune cells and increase Mtb proliferation; (8) commensal species (e.g., Lactobacillus plantarum) and microbiota metabolites (e.g., indole propionic acid) reduce tuberculosis progression; and (9) fecal transplants mostly restored eubiosis, increased immune resistance to Mtb, restricted dissemination of Mtb, and reduced tuberculosis-associated organ pathologies. Overuse of antimicrobials, as shown in mice, is a risk factor for reactivating latent or treated tuberculosis.

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Section: Antimicrobials Microbiome Immunity and Mtbmentioning

confidence: 93%

Section: Metabolites-immunitymentioning

confidence: 97%

Section: Immunity (Autophagy)-microbiome Interactionsmentioning

confidence: 99%

Section: Mtb-microbiome Interactionsmentioning

confidence: 99%

Section: Antimicrobials Microbiome Immunity and Mtbmentioning

confidence: 99%

See 3 more Smart Citations

Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Sekyere

Maningi

Fourie

2020

Annals of the New York Academy of Sciences

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Short-Chain Fatty Acids Promote Mycobacterium avium subsp. hominissuis Growth in Nutrient-Limited Environments and Influence Susceptibility to Antibiotics

2020

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Mycobacterium avium subsp. hominissuis (MAH) is a common intracellular pathogen that infects immunocompromised individuals and patients with pre-existing chronic lung diseases, such as cystic fibrosis, who develop chronic and persistent pulmonary infections. The metabolic remodeling of MAH in response to host environmental stresses or within biofilms formed in bronchial airways plays an important role in development of the persistence phenotype contributing to the pathogen’s tolerance to antibiotic treatment. Recent studies suggest a direct relationship between bacterial metabolic state and antimicrobial susceptibility, and improved antibiotic efficacy has been associated with the enhanced metabolism in bacteria. In the current study, we tested approximately 200 exogenous carbon source-dependent metabolites and identified short-chain fatty acid (SCFA) substrates (propionic, butyric and caproic acids) that MAH can utilize in different physiological states. Selected SCFA enhanced MAH metabolic activity in planktonic and sessile states as well as in the static and established biofilms during nutrient-limited condition. The increased bacterial growth was observed in all conditions except in established biofilms. We also evaluated the influence of SCFA on MAH susceptibility to clinically used antibiotics in established biofilms and during infection of macrophages and found significant reduction in viable bacterial counts in vitro and in cultured macrophages, suggesting improved antibiotic effectiveness against persistent forms of MAH.

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Microbial Short Chain Fatty Acids Impair Mycobacterium Avium (MAC) Clearance by Alveolar Macrophages

Cited by 2 publications

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Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Short-Chain Fatty Acids Promote Mycobacterium avium subsp. hominissuis Growth in Nutrient-Limited Environments and Influence Susceptibility to Antibiotics

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