Microbiota and the immune system: how the gut microbiome influences resistance to infection

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection affect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology.

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Sepsis and the Microbiome: A Vicious Cycle

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa682 ◽

2020 ◽

Author(s):

William D Miller ◽

Robert Keskey ◽

John C Alverdy

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Enteral Feeding ◽

Gut Microbiome ◽

Antibiotic Stewardship ◽

Vicious Cycle ◽

Fecal Transplant ◽

Suspected Infection

Abstract Although sepsis has been characterized as a dysregulated immune response to an ongoing or suspected infection, the role of the microbiome as a key influencer of the septic response is emerging. The unavoidable disruption of the microbiome while treating sepsis with antibiotics can itself result in immune system dysregulation, further exacerbating the course and outcome of sepsis. Alterations in the gut microbiome as a result of sepsis and its treatment have been implicated in the organ dysfunction typical of sepsis across a wide variety of tissues including the lung, kidney and brain. A number of microbiota directed interventions are currently under investigation in the setting of sepsis including fecal transplant, the administration of dietary fiber in enteral feeding products and the use of antibiotic scavengers that are directed at attenuating the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. Taken together, the emerging role of the gut microbiome in sepsis touches various elements of the pathophysiology of sepsis and its treatment, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.

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The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

International Journal of Cancer ◽

10.1002/ijc.31836 ◽

2018 ◽

Vol 144 (10) ◽

pp. 2365-2376 ◽

Cited By ~ 8

Author(s):

Kate R. Secombe ◽

Janet K. Coller ◽

Rachel J. Gibson ◽

Hannah R. Wardill ◽

Joanne M. Bowen

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Innate Immune System ◽

Gastrointestinal Toxicity ◽

Innate Immune

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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

Journal of Visualized Experiments ◽

10.3791/59773 ◽

2019 ◽

Cited By ~ 4

Author(s):

Lance Daharsh ◽

Jianshui Zhang ◽

Amanda Ramer-Tait ◽

Qingsheng Li

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Mice Model ◽

Human Immune System ◽

Human Immune ◽

Blt Mice

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Gut Microbiome and Its Interaction with Immune System in Spondyloarthritis

Microorganisms ◽

10.3390/microorganisms8111727 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1727

Author(s):

Jacqueline So ◽

Lai-Shan Tam

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Current Evidence ◽

Future Research ◽

Hla B27 ◽

Human Immune System ◽

Gut Inflammation ◽

Germ Free ◽

Gut Microorganisms

Emerging evidence suggests there is a gut-joint axis in spondyloarthritis (SpA). In a study, subclinical gut inflammation occurred in nearly 50% of SpA. Chronic gut inflammation also correlated with disease activity in SpA. Trillions of microorganisms reside in the human gut and interact with the human immune system. Dysbiosis affects gut immune homeostasis and triggers different autoimmune diseases including SpA. The absence of arthritis in HLA-B27 germ-free mice and the development of arthritis after the introduction of commensal bacteria to HLA-B27 germ-free mice proved to be the important role of gut bacteria in shaping SpA, other than the genetic factor. The recent advance in gene sequencing technology promotes the identification of microorganisms. In this review, we highlighted current evidence supporting the link between gut and axial SpA (axSpA). We also summarized available findings of gut microbiota and its interaction with the immune system in axSpA. Future research may explore the way to modulate gut microorganisms in axSpA and bring gut microbiome discoveries towards application.

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The Multifaceted Effects of Gut Microbiota on the Immune System of the Intestinal Mucosa

Immuno ◽

10.3390/immuno1040041 ◽

2021 ◽

Vol 1 (4) ◽

pp. 583-594

Author(s):

Takehiro Hirano ◽

Hiroshi Nakase

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Gut Microbiome ◽

Mucosal Barrier ◽

Host Immune System ◽

Immunological Responses ◽

Gut Homeostasis ◽

Inflammatory Processes ◽

And Oxidative Stress

The gut microbiota has diverse microbial components, including bacteria, viruses, and fungi. The interaction between gut microbiome components and immune responses has been studied extensively over the last decade. Several studies have reported the potential role of the gut microbiome in maintaining gut homeostasis and the development of disease. The commensal microbiome can preserve the integrity of the mucosal barrier by acting on the host immune system. Contrastingly, dysbiosis-induced inflammation can lead to the initiation and progression of several diseases through inflammatory processes and oxidative stress. In this review, we describe the multifaceted effects of the gut microbiota on several diseases from the perspective of mucosal immunological responses.

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Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

10.1101/749093 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lance Daharsh ◽

Amanda E. Ramer-Tait ◽

Qingsheng Li

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Human Disease ◽

Humanized Mice ◽

Rrna Gene ◽

Human Immune System ◽

Human Gut ◽

Healthy Human ◽

Human Immune

AbstractBackgroundHumanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.ResultsSurgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.ConclusionsHere, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.

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Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

10.1101/487652 ◽

2018 ◽

Author(s):

Stacey L. Burgess ◽

Jhansi L. Leslie ◽

Md. Jashim Uddin ◽

Noah Oakland ◽

Carol Gilchrist ◽

...

Keyword(s):

Bone Marrow ◽

Gut Microbiome ◽

Bile Salts ◽

Parasite Infection ◽

Innate Immune ◽

Commensal Bacteria ◽

Immune Memory ◽

Intestinal Bacterium ◽

Subsequent Infection ◽

Resistance To Infection

AbstractThe gut microbiome provides resistance to infection. However, the mechanisms for this are poorly understood. Colonization with the intestinal bacterium Clostridium scindens provided protection from the parasite Entamoeba histolytica via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte-progenitors (GMPs) and provided neutrophil-mediated protection against subsequent challenge with E. histolytica. Adoptive transfer of bone-marrow from C. scindens colonized-mice into naïve-mice protected against ameba infection and increased intestinal neutrophils. Because of the known ability of C. scindens to metabolize the bile salt cholate, we measured deoxycholate and discovered that it was increased in the sera of C. scindens colonized mice, as well as in children protected from amebiasis. Administration of deoxycholate alone (in the absence of C. scindens) increased the epigenetic mediator JMJD3 and GMPs and provided protection from amebiasis. In conclusion the microbiota was shown to communicate to the bone marrow via microbially-metabolized bile salts to train innate immune memory to provide antigen-nonspecific protection from subsequent infection. This represents a novel mechanism by which the microbiome protects from disease.One Sentence SummaryIntroduction of the human commensal bacteria Clostridium scindens into the intestinal microbiota epigenetically alters bone marrow and protects from future parasite infection.

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