Skip to content

Immune System interplay with the Microbiome

The influence of the gut microbiome on the immune system, and the immune system's role in shaping the gut microbiome. Including the effects of vaccines


Review, Feb 2021: Diversity and dynamism of IgA−microbiota interactions

Immune response, not acute viral infections, responsible for neurological damage (Feb 2024, mice) Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity.

IL-17 controls central nervous system autoimmunity through the intestinal microbiome (Feb 2021)

Crosstalk between cells allows Listeria bacteria to hijack immune system IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection (June 2019, mice).

Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System (Jan 2021) "This study addressed this knowledge gap by identifying relationships between distinct bacterial taxa and cytokine responses to specific microbial agonists across highly diverse settings. Furthermore, we provide evidence that immunomodulatory effects of region-specific stool microbiomes can be partially recapitulated in germfree mice"

Impact of immune system:

How the immune system maintains a healthy gut microbiota. "We have identified a molecule, c-Maf, which is critical for the development and function of specific regulatory T cells in the gut. C-Maf prevents the immune system from attacking the microbiota. These results show that both the immune system and the microbiota mutually contribute to establishing and maintaining the balance in the gut" (2019): -

Immune system defects seem to contribute to obesity in mice. T cell–mediated regulation of the microbiota protects against obesity (July 2019) "healthy mice have plenty of Clostridia—a class of 20 to 30 bacteria—but those with an impaired immune system lose these microbes from their gut as they age. Even when fed a healthy diet, the mice inevitably become obese. Giving this class of microbes back to these animals allowed them to stay slim"

Genetic differences in the immune system shape the microbiome. Polymorphic immune mechanisms regulate commensal repertoire (Oct 2019, mice)

The interaction between iNKT cells and the mucosal microbiota (2018): - "Here we outline the influence the mucosal microbiota can have on iNKT cells, and how iNKT cells contribute to the maintenance of the microbiota composition"

Gut microbiota utilize immunoglobulin A for mucosal colonization (2018): - By wrapping itself in antibodies, this bacterium may become a stable, beneficial part of the gut. Without IgA, the microbes fail to permanently colonize the gut.

IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria (2018): Host antibodies shape gut microbiome by changing bacteria gene expression. Antibodies secreted in the gut promote the growth of beneficial bacteria. Immunoglobulin A (IgA) antibodies can alter the expression of bacterial genes, allowing different bacterial species to cooperate with each other and form a community that can protect the body from disease.

By using genetically modified mice, we showed that IgA-deficiency caused the expansion of certain members of commensal bacteria in the gut. Thus, IgA is functioning not only to protect us from harmful pathogens but also to maintain the commensal gut microbiota in mice and humans. (2018):

Review, 2018: IgA Responses to Microbiota:

Spleen development is modulated by neonatal gut microbiota (2018): - milk ?Secretory Immunoglobulin A (SIgA) regulates bacterial colonization of the newborn intestine

The immune cells of mucosal immune system – which is stretched throughout the length of gastrointestinal tract – harbor a wide array of pattern-recognition receptors (e.g. Toll-like receptors) and are in active cross-talk with the rest of immune system through the local mesenteric lymph nodes [63]. (2018):

Absence of NOD2 receptor predisposes to intestinal inflammation by a deregulation in the immune response in hosts that are unable to control gut dysbiosis (2018, mice):

Evidence for the Role of the Cecal Microbiome in Maintenance of Immune Regulation and Homeostasis (2018): IgM specifically affected mucosa-associated microbes, and that the affect was causal and not an epiphenomenon

Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation (2018): "These findings suggest that MAIT cells can discriminate and categorize complex human microbiota through computation of TCR signals depending on antigen load and presenting cells, and fine-tune their functional responses."

Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis (2018): "our findings illustrate a critical role for STAT3/Th17 in the containment of C. albicans as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities"

The host intestinal immune system is highly regulated by a complex interplay of various lymphoid tissues, immune cells, cytokines, and their receptors and possesses three distinct layers: mucus, epithelia, and lamina propria. These interacting layers play a large role in maintaining the microbiota and host immune system in homeostasis as well as regulating infection, inflammation, and autoimmunity (2018): "Norovirus interactions with the commensal microbiota"

The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis (2018):

Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice (2018):

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases (2019):

Antigen-presenting ILC3 regulate T cell–dependent IgA responses to colonic mucosal bacteria (2019):

Impact of gut microbiome on immune system:

Review, 2022: The early-life gut microbiome and vaccine efficacy

Review, 2018: Systemic instruction of cell-mediated immunity by the intestinal microbiome "In this commentary, we highlight some key studies that are beginning to broadly examine the different mechanisms by which the gastrointestinal microbiome can impact the systemic immune compartment"

Review, 2018: Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer

Review, 2018: Gut microbiota, cannabinoid system and neuroimmune interactions: New perspectives in multiple sclerosis The gut microbiota plays a fundamental role on the education and function of the host immune system. In this review, we gather the knowledge on the gut microbiota-endocannabinoids interactions and their impact on autoimmune disorders.

Review, 2018: Modulation of the immune system by the gut microbiota in the development of Type 1 Diabetes

Review, 2018: The role of the microbiota in infectious diseases

Review, 2018: The interplay between neutrophils and microbiota in cancer

Review, 2018: An insight into the intestinal web of mucosal immunity, microbiota, and diet and their role in inflammation and infection

Review, 2017: Human Virome "the findings so far indicate that the regulation of the immune response by viruses and other members of the microbiome can affect the outcome of infections"

Gut Microbiota Protect against Viral Infections by Keeping the Immune System Alert. "Moreover, it uncovers an underappreciated risk of antibiotic use during viral infections" (May 2022, mice) The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis

Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies (Feb 2021)

Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection. Colonization resistance is mediated through the bile salt hydrolase enzyme activity. Microbiome-dependent infection resistance can be restored through co-transplantation (Jun 2020)

The gut microbiota is associated with immune cell dynamics in humans (Nov 2020) "revealing a considerable influence of the gut microbiota—together and over time—on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity"

Study in mice demonstrates how gut bacteria help ward off viruses to make animals resistant to infection (Nov 2020) Commensal Microbiota Modulation of Natural Resistance to Virus Infection

Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility (Oct 2020)

Mucosal or systemic microbiota exposures shape the B cell repertoire (Aug 2020, mice)

The microbiome controls immune system fitness. The cells effectively lack the fuel needed to respond to pathogens. (May 2020, mice) Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells.

Commensal Bacteria Modulate Immunoglobulin A Binding in Response to Host Nutrition (Apr 2020)

MAIT cells are imprinted by the microbiota in early life and promote tissue repair (Oct 2019) "Mucosal-associated invariant T (MAIT) cells are absent in germ-free mice. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens."

How a healthy microbiome could supercharge the body's natural cancer-fighting cells. Particular [gut] microbiota metabolites enhanced the ability of killer cells to survive & form memory cells. These SCFAs change the way that the killer utilize fuels for energy generation (Jul 2019, mice) Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8+ T Cells.

Gut microbes produce compounds that prime immune cells to destroy harmful viruses in the brain and nervous system, according to a mouse study. The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling (July 2019)

The existence of certain microorganisms in your gut may bolster the immune system's ability to fend off a herpes viral attack that can cause fatal brain inflammation. Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis (May 2019)

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult. Once the microbiota is destroyed by antibiotics, the immune reaction no longer occurs (Mar 2019): -

A specific human-associated gut microbe, Clostridium orbiscindens, produced metabolite that protects mice from influenza through type I interferon (2017): "Specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN"

Recent research has shown that the immune system of infants is also in development during early years and not inborn as previously assumed (Simon et al., 2015). In a twin study, researchers dispelled the belief that the body’s immune system is genetically programmed (Brodin et al., 2015).

Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity (2004):

Bacterial secretion of histamine within the gut influences immune responses within the lung. (2018):

The intestinal microbiota regulates extra-intestinal immunity via the common mucosal immune system (2018): Upper Respiratory Symptoms, Gut Health and Mucosal Immunity in Athletes.

Regulation of inflammation by microbiota interactions with the host (2017): "Intestinal microbiota influence host response to infection"

Here we defined a role for the microbiota in modulating the immune response in a way that reduces inflammation and limits the damage it can do to the gut. The attachment of bacteria to the epithelium was not causing disease; on the contrary, it was necessary to promote a balanced regulation of the T cell responses and helped protect the gut (2018): | Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism (2018): - Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.

Autism Risk Determined by Health of Mom’s Gut, UVA Research Reveals. "as a result of microflora-associated calibration of gestational IL-17a (inflammatory molecule interleukin-17a) responses" (2018):

Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes (2018):

Intestinal Microbiota Disruption Reduces Regulatory T Cells and Increases Respiratory Viral Infection Mortality Through Increased IFNγ Production (2018):

Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation (2018): Altogether, our work highlights immune cell-epithelial cell interactions triggered by the microbiota that control intestinal immunity, epithelial differentiation, and carcinogenesis.

We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response. (2018):

gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis. "Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis (2018)"

Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes (2018):

Gut microbiome regulates the intestinal immune system, researchers find. - Commensals Suppress Intestinal Epithelial Cell Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis (2018):

"mice that received microbes from non-allergic infants expressed different genes compared to those that did not, suggesting that microbes residing in the gut impact the host’s immune system"

Microorganisms in the human gut can affect immune-system cells. Gut bacterial strains have been discovered that boost immune cells that have cell-killing capacity and that can target cancer and protect against infection. (2019): A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.

Fungus from the intestinal mucosa can affect lung health. With this observation, we were able to show for the first time how a single member of the microbiome, Candida albicans, influences the specific immune response to a large group of other microbes (Feb 2019) Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans.

Gut microbiota: Neonatal gut microbiota induces lung immunity against pneumonia (2017): - IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor (2017):

"Our study demonstrates that a host protein made in the intestine following exposure to the microbiota affects innate immune cell populations, both in the gut and other tissues" - Intestinal serum amyloid a suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization (2019):

Intestinal microbes influence development of thymic lymphocytes in early life (Jan 2020)


Rectal Microbiome Composition Correlates with Humoral Immunity to HIV-1 in Vaccinated Rhesus Macaques (Dec 2019) - Specific genus decreased after vaccination, and higher levels of certain genus were correlated with weaker or stronger immune responses.

Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response (Apr 2022, mice) "skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV and influence the host response to vaccination"

Gut microbiome influence on vaccines:

Review, 2023: Influence of Microbiota on Vaccine Effectiveness: “Is the Microbiota the Key to Vaccine-induced Responses?”

Review, 2022: Impact of the Host Microbiome on Vaccine Responsiveness: Lessons Learned and Future Perspective

Review, 2020: The Impact of the Microbiome on Immunity to Vaccination in Humans

Review, 2018: The influence of the intestinal microbiome on vaccine responses

Review, 2018: Role of nutrition, infection, and the microbiota in the efficacy of oral vaccines "seems likely that oral vaccine failure in resource-poor regions is affected by alterations to the immune response driven by dysbiotic changes to the microbiota"

Review, 2018: The Significance of the Intestinal Microbiome for Vaccinology: From Correlations to Therapeutic Applications

Review, 2018: The potential of the microbiota to influence vaccine responses. "emerging evidence [...] suggests that the gut microbiome plays a key role in shaping systemic immune responses to both orally and parenterally administered vaccines" - via sci-hub:

Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants (Dec 2021, n=122)

Gut Microbes Boost Flu Vaccine’s Success: Clinical Trial. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans (Sep 2019)

Gut Bacteria from Breastfeeding Linked to Improved Infant Response to Vaccines (June 2019)

Influence of non-polio enteroviruses and the bacterial gut microbiota on oral poliovirus vaccine response: a study from south India (Sept 2018): "Enteric viruses have greater impact on OPV response than the bacterial microbiota with recent enterovirus infections having greater inhibitory effect than persistent infections"

Antibiotic prescriptions in infants may impact the effectiveness of important vaccinations. "not the antibiotic exposure per se that causes the problem, but the recolonisation by abnormal microbiota after antibiotic exposure". Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice (2018)

Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines (2018):

Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial. (2018) - "In a proof-of-concept study in healthy adult men, scientists in the Netherlands found that microbiome manipulation with antibiotics influenced the response to oral rotavirus vaccine. Specifically, they found higher levels of viral shedding in those receiving antibiotic treatment prior to vaccination compared with controls receiving no antibiotic treatment prior to vaccination. The study is a human demonstration that altering the bacterial intestinal microbiome can affect a vaccine's immunogenicity."

Impact of vaccines on the microbiome:

Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children (2014): This study illustrates the much broader effect of vaccination with PCV-7 on the microbial community than currently assumed, and highlights the need for careful monitoring when implementing vaccines directed against common colonizers.

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice (2014): LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus.

Rob Knight 2017 talk, audience member asks about vaccines:

Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status (2018):

Microbial composition of the human nasopharynx varies according to influenza virus type and vaccination status (July 2019)"We observe that vaccination status, especially in more senior individuals, also has an association with the microbial community profile"