Gut Immune Cells Research Articles

Cefdinir Microsphere Modulated Microflora and Liver Immunological Response to Diet Induced Diabetes in Mice.

Gut microbiota is currently targeted for various diseases especially metabolic disorders such as diabetes. Our strategy is to alter gut microflora via specific antibiotic to reduce load of inflammation in the liver that increases as a result of high carbohydrate diet. Th1, Th17 and Treg are important immune cell types which decide the type of inflammatory response. Liver is tolerogenic in nature with low Th17/Treg ratio. In diabetics, this ratio decreases even more, and can cause liver trauma. The present study tries to find relationship between gut flora and immune cells such as Th1/Th17/Treg and their role in liver metabolism using diet induced diabetic mice model. Upon alteration of flora using Cefdinir in different forms, one could help lower the level of Treg cells thus increasing the ratio. Gut flora is strongly associated with the immunity in the liver. Targeted alteration of gut flora helps us to restore insulin sensitivity. Colon targeted Cefdinir gives more promising results, opens colonic bacteria as target for improving gut, liver inflammation and insulin sensitivity.

Lymphocytes mediate bone loss induced by gut microbiota repopulation following antibiotic use

Recent studies link the gut microbiota, immune cells and bone health. We identified that treatment of mice with oral antibiotics followed by four weeks of natural repopulation leads to an altered gut microbiota composition as well as bone loss. To identify the role of lymphocytes in post‐ABX repopulation induced bone loss, we treated T and B lymphocyte‐deficient Rag knockout mice and corresponding wild‐type (WT) mice (male, C57BL/6J, 12 weeks of age) with antibiotics (ABX, ampicillin (1g/L) and neomycin (0.5g/L)) in the water for two weeks. Afterwards, mice received water without antibiotics for another 4 weeks to allow the repopulation of gut microbiota. Bone volume fraction (BVF) of the femurs were analyzed using microcomputed tomography. Our results demonstrate a significant decrease in post‐ABX WT mouse femoral trabecular BVF (relative to body weight (BW)) (WT:0.98±0.05, WT‐ABX: 0.69±0.07, n=14–17). Strikingly, this effect was not observed in the RAG‐KO (BVF/BW KO: 1.57±0.07, KO‐ABX: 1.49±0.11, n=9–11) mice. Analysis by diversity metrics (Bray‐Curtis) showed similar changes in gut microbiota repopulation in both the WT and RAG‐KO group. However, several operational taxonomic units (OTUs) classified as Lactobacillales were significantly higher in the repopulated RAG‐KO group when compared to the WT group (WT‐ABX: 0.24±.07, KO‐ABX:2.63±.31, n=11–14). This suggests that Lactobacillales might play a protective role in preventing bone loss during post‐ABX repopulation in the RAG‐KO mice. To test this possibility, we administered Lactobacillus reuteri 6475 for 4 weeks to post‐ABX‐treated WT mice. Our data establish that Lactobacillus reuteri 6475 can colonize the gut in the WT mice and more importantly, it prevents bone loss induced by post‐ABX repopulation. Together, our results demonstrate an important role for lymphocytes in regulating bone health and for the role of Lactobacillus reuteri 6475 to prevent bone loss in ABX‐treated mice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Taurine on Intestinal Microbiota and Immune Cells in Peyer's Patches of Immunosuppressive Mice.

Taurine is a sulfur-containing amino acid which has strong activities in enhancing immunity. Gut microbiota is closely interrelated with intestinal mucosal immunity, but the effects and mechanisms of taurine on intestinal microbiota and mucosal immune cells under an immunosuppressive condition remain unclear. This study was conducted to investigate the effect of taurine on gut microbiota and immune cells in Peyer's patches (PPs) of dexamethasone (Dex)-induced immunosuppressive mice. Mice (4-week-old, Male) were randomly divided into three groups: the Control group (n=12), the Dex-induced immunosuppressive model group (n=12) and the taurine intervention group (n=12). The model was established by Dex injection for 7days and the taurine intervention group was gavaged 100mg/kg soluble taurine for 30days. The changes of intestinal microbiota and immune cells in PPs were tested by denaturing gradient gel electrophoresis (DGGE) and flow cytometry, respectively. Results showed that the microbiota in immunosuppressive mice was obvious different compared with control group, in which, the Lachnospiraceae and Ruminococcaceae groups were significantly reduced, and their reduction were reversed after taurine intervention. Compared to the control group, the total cell number in PPs, as well as the subsets of CD3+ cells (T cells), CD19+ cells (B cells) in model groups were significantly lower, and they were dramatically improved after taurine treatment. Our results suggested that taurine has a positive effect on i ntestinal homeostasis of the immunosuppressive mice.

Microbiota in the Gastrointestinal Tract.

Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and varying environmental conditions, e.g., diets, antigen exposure, infections, or medication, as well as genetics, age, or hygiene factors, strongly influence the bacterial community. A fine interaction between the host and microbiota determines the outcome of health or disease. The gut immune system is constantly challenged to distinguish between commensal non-invasive bacteria and potential pathogens. Goblet cells produce mucins that prevent most gut bacteria from penetrating through intestinal epithelial barrier, and Paneth cells are the main supplier of anti-microbial defensins. Gut epithelial and immune cells recognize bacteria via surface markers and they initiate an adequate immune answer. A dysbiosis is noticed in several diseases, but the crucial role in pathogenesis has to be proven. Prebiotics or probiotics are discussed as valuable tools to preserve or restore a healthy gut community.

Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells.

Background & AimsPsoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS).MethodsWe applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease.ResultsWe first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non–cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis.ConclusionsThese results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin–gut interaction provides new insights into the coincidence of psoriasis and IBD.

Inflammation and intestinal leakiness in older HIV+ individuals with fish oil treatment

Fish oil is a natural product that has shown efficacy for managing inflammatory conditions with few side effects. There is emerging evidence that crosstalks between gut epithelial cells and immune cells contribute to chronic infectious diseases. HIV-infected (HIV+) older adults show age-related co-morbidities at a younger age than their uninfected counterparts. Persistent inflammation related to the chronic viral infection and its sequelae is thought to contribute to this disparity. However, little is known about whether fish oil reduces intestinal inflammation in HIV + patients. We measure inflammation and gut barrier function in HIV + older adults (median age = 52, N = 33), following 12 weeks of fish oil supplementation (a total daily dose of 1.6 g of omega-3 fatty acids). We showed a reduction in inflammation and gut permeability as measured by CD14, inflammatory cytokines, lipopolysaccharide, and lipopolysaccharide binding protein. The results indicate that older HIV + adults may benefit from a diet supplemented with the omega-3 fatty acids found in fish oil.

32 Impact of colibactin-producing escherichia coli on immune microenvironment in preclinical colorectal cancer models

IntroductionIncreasing evidence link the immune microenvironment, microbiota and colorectal cancer (CRC). E. coli pks+ are more frequently detected on CRC patient mucosa and exhibit procarcinogenic properties in CRC murine models. Aim of this work was to evaluate the impact of chronical infection by colibactin-producing E. coli on immune cells in APCmin/+ mice colon.Material and methodsMin mice were per os inoculated with a CRC E. coli pks+ strain (11 G5), non-pathogenic E. coli (K-12) or PBS. Induction of oxidative stress and inflammation during the infection was evaluated using optical in vivo imaging (IVIS spectrum). After 7 weeks, number and volume of polyps were evaluated and colonic samples were histologically analysed. Immunofluorescent staining of immune cells (neutrophils and T cell populations) was performed to quantify positive cells in three interesting colon areas: mucosa, lymphoid follicle and tumour using an innovative algorithm created with Tissue Studio software. In parallel, quantification of immune cells (lymphoid populations) was performed in mesenteric lymph node (MLNs) by flow cytometry.Results and discussionsUsing optical imaging, we detected a significant increase of oxidative stress and inflammation in the gut after thirty days of 11 G5 infection. However, using our specific algorithm and CD45 immunostaining, we observed a significant increase of lymphoid follicle size in the gut of mice infected with the 11 G5 strains. Interestingly, follicle size was positively correlated with tumour volume suggesting an association between pro-carcinogenic properties of 11 G5 strain and gut immune response. In addition, we observed an increase of neutrophils on the mucosa and lymphoid follicle of 11 G5 infected mice. These results can be linked to our in vivo optical imaging observations. Moreover we observed a trend to decrease of CD3+ T cells on mucosa and tumour for the 11 G5 group, suggesting a possible link between E. coli pks +and anti-tumour T cells. Finally we noticed a significant decrease of CD4+ CD25+ anti-inflammatory T cells in MLNs of 11 G5 infected mice, negatively correlated with gut bacteria colonisation.ConclusionHere we report a potential immunomodulatory effect on gut microenvironment by pks+E. coli, which could be associated with its carcinogenic effect. Our results suggest that gut lymphoid follicle and immune cells such as neutrophils and T cells could be involved in this process. This work shows a link between immune microenvironment, pathogenic E. coli and tumour development.

Immunomodulation by food: impact on gut immunity and immune cell function.

Recent studies have revealed that various food components affect the immune response. These components act on various immune cells, and their effects are mediated through the intestinal immune system and, in some cases, the intestinal microbiota. In this review, we describe the immunomodulating effects of various food components, including probiotics, prebiotics, polysaccharides, vitamins, minerals, fatty acids, peptides, amino acids and polyphenols. Some of these components enhance immune responses, leading to host defense against infection, whereas others inhibit immune responses, thus suppressing allergy and inflammation.

CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi.

Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn's disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

Phagocytes patrol intestinal fungi

Gut Immunity Maintaining a healthy balance of gut bacteria can promote good health. Leonardi et al. show that fungi can also interact with gut immune cells to maintain intestinal well-being. CX3CR1+ mononuclear phagocytes (MNPs) patrol the intestine and promote antifungal immunity. Genetic deletion

Δ9-tetrahydrocannabinol (THC) activation of cannabinoid receptors induces unique changes in the murine gut microbiome and associated induction of myeloid-derived suppressor cells and Th17 cells.

Abstract Δ9-tetrahydrocannabinol (THC) is a partial agonist for cannabinoid receptors (CB1 & CB2), is the main psychoactive ingredient found in the Cannabis plant, and can modulate the nervous and immune system. Our intestine harbors a diverse array of bacteria, referred to as the microbiome, which is known to impact many bodily functions, including the immune system. In the current study, we investigated the effect of THC on the gut microbiome and the naïve immune response. We tested the effect of acute or chronic exposure of C57BL/6 mice to THC on the immune system, and correlated said changes with a flux in intestinal bacteria. Intraperitoneal exposure to THC resulted in migration of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) from the bone marrow to the peritoneal cavity. These MDSCs remained in the peritoneum throughout chronic THC administration, where they proliferated and produced IL-6. The peritoneal IL-6 led to an increase in T helper 17 (Th17) cells in the mesenteric lymph node (mLN), as well as increases of IL-17A in the serum and mLN supernatant of THC-treated mice. Indeed, an adoptive transfer of THC MDSCs increased the number of Th17 cells compared to bone marrow (BM) MDSCS, and in-vitro polarization experiments revealed THC MDSCs to be more potent inducers of Th17 cells than BM MDSCs. The alterations in the gut immune cells occurred in tandem with an increase in the number of Alphaproteobacteria in the cecum and feces of mice treated with THC compared to vehicle and naïve mice, and this effect was replicated after an adoptive transfer of THC MDSCS, but not BM MDSCs. Together, these data demonstrated that marijuana use can alter the gut microbiota as well as cause significant changes in the naïve immune system.

Endocannabinoid system acts as a regulator of immune homeostasis in the gut

Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2. We show that the engagement of the cannabinoid/vanilloid receptors augments the number and immune suppressive function of the regulatory CX3CR1hi macrophages (Mϕ), which express the highest levels of such receptors among the gut immune cells. Additionally, TRPV1-/- or CB2-/- mice have fewer CX3CR1hi Mϕ in the gut. Treatment of mice with CP also leads to differentiation of a regulatory subset of CD4+ cells, the Tr1 cells, in an IL-27-dependent manner in vitro and in vivo. In a functional demonstration, tolerance elicited by engagement of TRPV1 can be transferred to naïve nonobese diabetic (NOD) mice [model of type 1 diabetes (T1D)] by transfer of CD4+ T cells. Further, oral administration of AEA to NOD mice provides protection from T1D. Our study unveils a role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and reveals a conversation between the nervous and immune systems using distinct receptors.

Probiotic Metabolites Promote Anti‐inflammatory Functions of Immune Cells

The microbiome is an important factor in human health and disease. Recent reports demonstrate that short‐chain fatty acids (SCFA), type of bacterial metabolites, ameliorate autoimmune diseases, indicating a link between the gut microbiome, immune cells and inflammation. In this study, we investigated the potential health benefits of probiotic bacterial metabolites by evaluating their functions in regulating the differentiation of anti‐inflammatory and pro‐inflammatory immune cells, and determining the underlying mechanisms.Using conditioned media from the probiotic bacteria, Lactococcus lactis and Lactobacillus reuteri, we demonstrated that bacterial metabolites induced differentiation of immunosuppressive anti‐inflammatory T‐regulatory (Treg) cells. Consistently, butyrate, a bacterial‐derived SCFA, enhanced the differentiation of Treg cells from naïve CD4+ T cells. Furthermore, butyrate inhibited the maturation of pro‐inflammatory antigen‐presenting dendritic cells (DCs) from hematopoietic progenitor cells. Mechanistically, we found that butyrate promoted Treg cell differentiation via increasing expression of transcription factor Foxp3 and the anti‐inflammatory cytokine IL‐10. In addition, it suppressed the maturation of DCs by inhibiting the expression of CD11c and MHC Class II, critical molecules for pathogenic CD4+ T cell activation. Taken together, these studies reveal novel functions of probiotic metabolites, SCFA, in regulating the differentiation/activation of anti‐inflammatory and pro‐inflammatory immune cells, thus inhibiting inflammation and promoting human health.Support or Funding InformationThis work was supported by the National Institute of Health grants NS057563 (E.N.B.)

Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions.

The relationship between host organisms and their microbiota has co-evolved towards an inter-dependent network of mutualistic interactions. This interplay is particularly well studied in the gastrointestinal tract, where microbiota and host immune cells can modulate each other directly, as well as indirectly, through the production and release of chemical molecules and signals. In this review, we define the functional impact of transforming growth factor-beta (TGF-β) on this complex interplay, especially through its modulation of the activity of local regulatory T cells (Tregs), type 17 helper (Th17) cells, innate lymphoid cells (ILCs) and B cells.

The aryl hydrocarbon receptor in T cells contributes to sustaining oral tolerance against ovalbumin in a mouse model.

Oral tolerance (OT) towards antigens encountered in the gut is a vital immune function of gut immunity. Experimental models can demonstrate OT efficacy by feeding of a protein followed by peripheral immunization and measuring the specific antibody titer. We had previously shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a xenobiotic high-affinity aryl hydrocarbon receptor (AhR)-ligand, destabilized OT against ovalbumin (OVA) in mice. AhR is involved in the development, differentiation and function of immune cells, and highly expressed in gut epithelial cells and gut immune cells. We here used AhR-deficient mice to study the role of AhR in OT further. We show that complete AhR-deficiency undermines the stability of oral tolerance against OVA upon multiple immunizations, despite no renewed oral encounter with the antigen. This OT destabilization is accompanied by significant changes in IL10 and TGFβ RNA in the gut tissue. Using conditional AhR-deficient mouse lines, we identify T cells as the major responsible immune cell type in this context. Our findings add to knowledge that lack of AhR signaling in the gut impairs important gut immune functions.

Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry.

Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders.

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance.

The intestinal epithelial lining is a very dynamic interface, where multiple interactions occur with the external world. The intestinal epithelial barrier is continuously exposed to a huge load of commensal microorganisms, food-borne antigens, as well as invading enteropathogens. Intestinal epithelial cells (IECs) and underlying immune cells are the main players in maintaining the delicate balance between gut tolerance and inflammation. IECs deferentially express the variety of chemokines and chemokine receptors, and these receptor-ligand interactions not only mediate the infiltration and activation of immune cells but also switch on the survival cascades in IECs. In this review, we discussed how chemokine-chemokine receptor-induced interactions play a central role to coordinate the interplay between IECs and gut immune cells to maintain homeostasis or elicit gut inflammation. Furthermore, we discussed how chemokines and chemokine receptors were used as a target for developing new drugs and therapies to control gut inflammation and autoimmunity.

Changes in enteroendocrine and immune cells following colitis induction by TNBS in rats.

Approximately 3.6 million individuals suffer from inflammatory bowel disease (IBD) in the western world, with an annual global incidence rate of 3–20 cases/100,000 individuals. The etiology of IBD is unknown, and the currently available treatment options are not satifactory for long-term treatment. Patients with inflammatory bowel disease present with abnormalities in multiple intestinal endocrine cell types, and a number of studies have suggested that interactions between gut hormones and immune cells may serve a pivotal role in the pathophysiology of IBD. The aim of the present study was to investigate alterations in colonic endocrine cells in a rat model of IBD. A total of 30 male Wistar rats were divided into control and trinitrobenzene sulfonic acid (TNBS)-induced colitis groups. Colonoscopies were performed in the control and TNBS groups at day 3 following the induction of colitis, and colonic tissues were collected from all animals. Colonic endocrine and immune cells in the obtained tissue samples were immunostained and their densities were quantified. The densities of chromogranin A, peptide YY, and pancreatic polypeptide-producing cells were significantly lower in the TNBS group compared with the control group, whereas the densities of serotonin, oxyntomodulin, and somatostatin-producing cells were significantly higher in the TNBS group. The densities of mucosal leukocytes, B/T-lymphocytes, T-lymphocytes, B-lymphocytes, macrophages/monocytes and mast cells were significantly higher in the TNBS group compared with the controls, and these differences were strongly correlated with alterations in all endocrine cell types. In conclusion, the results suggest the presence of interactions between intestinal hormones and immune cells.

Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis.

Epidemiological studies have linked increased incidence of inflammatory diseases and intestinal cancers in the developed parts of the world to the consumption of diets poor in dietary fibers and rich in refined carbohydrates. Gut bacteria residing in the intestinal lumen exclusively metabolize dietary fibers. Butyrate, propionate and acetate, which are collectively called short-chain fatty acids (SCFAs), are generated by fermentation of dietary fibers by gut microbiota. Evidences indicate that SCFAs are key players in regulating beneficial effect of dietary fibers and gut microbiota on our health. SCFAs interact with metabolite-sensing G protein-coupled receptors GPR41, GPR43 and GPR109A expressed in gut epithelium and immune cells. These interactions induce mechanisms that play a key role in maintaining homeostasis in gut and other organs. This review summarizes the protective roles of GPR41, GPR43 and GPR109A in dietary fibers-, gut microbiota- and SCFAs-mediated suppression of inflammation and carcinogenesis in gut and other organs.

Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota.

As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D). Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.