Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

Jourdan E. Lakes; Xu Fu; Brock T. Harvey; Khaga R. Neupane; Surya P. Aryal; Jessica L. Ferrell; Michael D. Flythe; Christopher I. Richards

doi:10.1016/j.anaerobe.2023.102787

Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

Jourdan E. Lakes, Xu Fu, Brock T. Harvey, Khaga R. Neupane, Surya P. Aryal, Jessica L. Ferrell, Michael D. Flythe, Christopher I. Richards

Research output: Contribution to journal › Article › peer-review

Abstract

Objectives: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. Methods: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B₁4, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. Results: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B₁4 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. Conclusions: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

Original language	English
Article number	102787
Journal	Anaerobe
Volume	83
DOIs	https://doi.org/10.1016/j.anaerobe.2023.102787
State	Published - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Ltd

Funding

JEL was supported by a National Institutes of Health , National Institute on Drug Abuse T32 Training Grant ( DA016176 ) and an appointment to the Agricultural Research Service (ARS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) under DOE contract number DE-SC0014664 . MDF was supported by the USDA , Agricultural Research Service National Program NP-215, Grass, Forage and Rangeland Agroecosystems. CIR was supported by the National Institute of Health ( R01GM138837 ).

Funders	Funder number
National Institutes of Health (NIH)	R01GM138837
Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory	DE-SC0014664
National Institute on Drug Abuse	DA016176
U.S. Department of Agriculture	NP-215
Oak Ridge Institute for Science and Education
USDA-Agricultural Research Service

Keywords

Cytokine response
Metabolism
Microbiota
Nicotine
Substance use disorder
Vesiculation

ASJC Scopus subject areas

Microbiology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.anaerobe.2023.102787

Cite this

@article{a35b9cdfec084e9587549876a870acbe,

title = "Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria",

abstract = "Objectives: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. Methods: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. Results: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. Conclusions: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.",

keywords = "Cytokine response, Metabolism, Microbiota, Nicotine, Substance use disorder, Vesiculation",

author = "Lakes, {Jourdan E.} and Xu Fu and Harvey, {Brock T.} and Neupane, {Khaga R.} and Aryal, {Surya P.} and Ferrell, {Jessica L.} and Flythe, {Michael D.} and Richards, {Christopher I.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = oct,

doi = "10.1016/j.anaerobe.2023.102787",

language = "English",

volume = "83",

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T1 - Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

AU - Lakes, Jourdan E.

AU - Fu, Xu

AU - Harvey, Brock T.

AU - Neupane, Khaga R.

AU - Aryal, Surya P.

AU - Ferrell, Jessica L.

AU - Flythe, Michael D.

AU - Richards, Christopher I.

PY - 2023/10

Y1 - 2023/10

N2 - Objectives: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. Methods: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. Results: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. Conclusions: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

AB - Objectives: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. Methods: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. Results: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. Conclusions: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

KW - Cytokine response

KW - Metabolism

KW - Microbiota

KW - Nicotine

KW - Substance use disorder

KW - Vesiculation

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DO - 10.1016/j.anaerobe.2023.102787

M3 - Article

C2 - 37827238

AN - SCOPUS:85173880130

SN - 1075-9964

VL - 83

JO - Anaerobe

JF - Anaerobe

M1 - 102787

ER -

Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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