• Granulomatous mastitis
• Immunity
• Macrophages
• Single-cell RNA sequencing
• T cells
• Tissue

• 2024CX023 the Innovative Projects for Graduate Students in Hunan Province
• 82474519 the National Natural Science Foundation of China
• 23A0291 the Project of Hunan Provincial Department of Education

• GBP1
• Immune response
• Liquid–liquid phase separation
• Machine learning
• Ulcerative colitis

• Humans
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/diagnosis
• Biomarkers/metabolism
• Gene Expression Profiling
• Male
• Female
• Cytokines/genetics
• Cytokines/metabolism
• Adult
• Phase Separation

• commensal to pathogen transition
• dysbiosis
• enterococcal-host interactions
• enterococci
• gastrointestinal tract
• inter-organ dissemination

• Weill Cornell Medicine
• Department of Defense
• June Allyson Memorial Fund Research Award
• Thomas Caputo Research Award

• Humans
• Gastrointestinal Microbiome
• Liver/microbiology
• Liver Diseases/microbiology
• Animals
• Gastrointestinal Tract/microbiology

• barrier integrity
• epithelial homeostasis
• immune signaling
• pathogen detection
• tissue repair

• Homeostasis
• Humans
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Animals
• Immunity, Innate
• Respiratory Mucosa/microbiology
• Respiratory Mucosa/immunology
• Epithelial Cells/microbiology
• Signal Transduction
• Adaptive Immunity
• Macrophages/immunology
• Macrophages/microbiology
• Host-Pathogen Interactions

• NADPH signalling pathway
• cardiovascular diseases
• natural products
• oxidative stress

• TLR
• Toll-like receptors
• epithelial barrier function
• host–bacterial interactions
• imiquimod
• intestinal permeability
• tight junctions

• liver diseases
• liver fibrosis
• liver lymphocyte homing
• low-grade inflammation
• microbiota
• microbiota-gut-liver axis
• non-alcoholic fatty liver disease (NAFLD)
• steatohepatitis (NASH)

• Humans
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/complications
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Fibrosis
• Immunity

• Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica

• Immunological microenvironment
• Inflammatory response
• Ischemia-reperfusion injury
• Liver
• Organ crosstalk
• Polytrauma

Myocarditis is the common cause of sudden cardiac death, dilated cardiomyopathy (DCM) and heart failure (HF) in young adults. The most common type of myocarditis is viral myocarditis (VMC). Toll-like receptors (TLRs) are vital to identify pathogens in vivo. TLRs promote the differentiation of naive CD4⁺T cells to T helper (Th) cells, activate the immune response, and participate in the pathogenesis of autoimmune and allergic diseases. Although the pathogenesis of VMC is unclear, autoimmune responses have been confirmed to play a significant role; hence, it could be inferred that VMC is closely related to TLRs and Th responses. Some drugs have been found to improve the prognosis of VMC by regulating the immune response through activated TLRs. In this review, we discuss the role of TLRs and Th responses in VMC.

• TLRs
• Th cells
• immune response
• regulatory T cell
• viral myocarditis

The gastrointestinal tract is a complex organization of various types of epithelial cells forming a single layer of the mucosal barrier, the host mucosal immune system, and microorganisms termed as gut microbiota inhabiting this area. The mucosal barrier, including physical and chemical factors, spatially segregates gut microbiota and the host immune system preventing the development of immune response directed towards non-pathogenic commensals and dietary antigens. However, for the maintenance of the integrity of the mucosal surfaces, cross-talk between epithelial cells and microbiota is required. The microbiome and the intestinal epithelium developed a complex dependence necessary for sustaining intestinal homeostasis. In this review, we highlight the role of specific epithelial cell subtypes and their role in barrier arrangement, the mechanisms employed by them to control intestinal microbiota as well as the mechanisms utilized by the microbiome to regulate intestinal epithelial function. This review will provide information regarding the development of inflammatory disorders dependent on the loss of intestinal barrier function and composition of the intestinal microbiota.

The gastrointestinal tract, which is constantly exposed to a multitude of stimuli, is considered responsible for maintaining the homeostasis of the host. It is inhabited by billions of microorganisms, the gut microbiota, which form a mutualistic relationship with the host. Although the microbiota is generally recognized as beneficial, at the same time, together with pathogens, they are a permanent threat to the host. Various populations of epithelial cells provide the first line of chemical and physical defense against external factors acting as the interface between luminal microorganisms and immunocompetent cells in lamina propria. In this review, we focus on some essential, innate mechanisms protecting mucosal integrity, thus responsible for maintaining intestine homeostasis. The characteristics of decisive cell populations involved in maintaining the barrier arrangement, based on mucus secretion, formation of intercellular junctions as well as production of antimicrobial peptides, responsible for shaping the gut microbiota, are presented. We emphasize the importance of cross-talk between gut microbiota and epithelial cells as a factor vital for the maintenance of the homeostasis of the GI tract. Finally, we discuss how the imbalance of these regulations leads to the compromised barrier integrity and dysbiosis considered to contribute to inflammatory disorders and metabolic diseases.

• Paneth cells
• epithelial cells
• gastrointestinal tract
• goblet cells
• microbiota

Human gut microbiota are involved in different metabolic processes, such as digestion and nutrient synthesis, among others. For the elderly, supplements are a major means of maintaining health and improving intestinal homeostasis. In this study, 51 elderly women were administered MPRO3 (n = 17), a placebo (n = 16), or both (MPRO3: 1 week, placebo: 3 weeks; n = 18) for 4 weeks. The fecal microbiota were analyzed by sequencing the 16S rRNA gene V3–V4 super-variable region. The dietary fiber intake increased, and glucose levels decreased with 4-week MPRO3 intake. Reflux, indigestion, and diarrhea syndromes gradually improved with MPRO3 intake, whereas constipation was maintained. The stool shape also improved. Bifidobacterium animalis, B. pseudolongum, Lactobacillus plantarum, and L. paracasei were relatively more abundant after 4 weeks of MPRO3 intake than in those subjects after a 1-week intake. Bifidobacterium and B. longum abundances increased after 1 week of MPRO3 intake but decreased when the intake was discontinued. Among different modules and pathways, all 10 modules analyzed showed a relatively high association with 4-week MPRO3 intake. The mineral absorption pathway and cortisol biosynthesis and secretion pathways correlated with the B. animalis and B. pseudolongum abundances at 4 weeks. Therefore, 4-week MPRO3 intake decreased the fasting blood glucose level and improved intestinal health and metabolism.

• 16S rRNA
• gut microbiota
• prebiotics
• probiotics
• synbiotics

• Esophageal reflux
• Gastroesophageal reflux disease
• Inflammation
• Inflammatory response
• Toll-like receptor 4

• calf
• colostrum
• innate immunity
• intestine

• E. coli
• Lactobacillus
• immunomodulation
• inflammation
• intestinal epithelial cells
• probiotics

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

• NAFLD
• RUNX1
• gut–liver axis
• jejunum
• liver
• metabolism

• COVID-19
• SARS-CoV-2
• immunity
• intestinal microbiota
• virus

To study the characteristics and relationship of the gut microbiota in patients with polycystic ovary syndrome (PCOS).

We recruited 45 patients with PCOS and 37 healthy women from the Reproductive Department of Shengjing Hospital. We recorded their clinical indexes, and sequenced their fecal samples by 16S rDNA full-length assembly sequencing technology (16S-FAST).

We found decreased α diversity and different abundances of a series of microbial species in patients with PCOS compared to healthy controls. We found LH and AMH were significantly increased in PCOS with Prevotella enterotype when compared to control women with Prevotella enterotype, while glucose and lipid metabolism level remained no significant difference, and situations were opposite in PCOS and control women with Bacteroides enterotype. Ruminococcus gnavus, Prevotella stercorea, Dialister succinatiphilus and Bacteroides fragilis were more abundant while Christensenellaceae spp. were less abundant in the PCOS group. P. stercorea was significantly more prevalent in PCOS-not insulin resistance (NIR) compared to control-NIR and PCOS-not overweight (NOW) patient groups compared to control-NOW groups. Kyoto Encyclopedia Genes and Genomes reflecting pathways related to lipopolysaccharide biosynthesis were more abundant in the PCOS group.

Our study found gut microbiota that had different abundance in patients with PCOS compared to healthy controls. An intimate relationship was shown between the gut microbiota and pathological changes in PCOS. We suggest the gut microbiota should be taken into consideration in the treatment of symptoms of PCOS via drugs and diet.

• 16S-FAST
• PCOS (polycystic ovarian syndrome)
• enterotype
• insulin resistance
• intestinal microbiome
• overweight

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4⁺T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

• American ginseng
• fecal metabolites
• gut barrier function
• gut microbiota
• immunostimulant

• ASD
• Astrocyte
• Gut microbiota
• Gut-brain axis
• Microglia
• Neuroinflammation

• Autism Spectrum Disorder/diet therapy
• Autism Spectrum Disorder/immunology
• Autism Spectrum Disorder/metabolism
• Brain/immunology
• Brain/metabolism
• Brain-Gut Axis/physiology
• Gastrointestinal Microbiome/physiology
• Humans
• Immunity, Cellular/physiology
• Microglia/immunology
• Microglia/metabolism
• Prebiotics/administration & dosage

• Esophageal adenocarcinoma
• Esophageal cancer
• Proliferation
• Statin
• Toll-like receptor 4

Human trichinellosis is acquired by eating raw or undercooked meats carrying muscle larvae of Trichinella spp. Toll-like receptors (TLRs) are essential components of the innate immune system. However, little is known about the potential application of TLR agonists for immunotherapy against Trichinella spiralis (T. spiralis) infection. Here, we evaluated the effects of four TLR agonists (i.e., TLR3, TLR4, TLR8, and TLR9 agonists) on T. spiralis infection in mice. The reduction rate of worm burden showed that TLR3 agonist poly(I:C) significantly reduced T. spiralis infection rather than TLR4, TLR8, and TLR9 agonists (p < 0.05). Moreover, TLR3 showed a continuous high-level of expression during 6–35 days post infection (dpi). The levels of interferon-gamma (IFN-γ), interleukin (IL)-2, and IL-6 increased significantly in mice serum compared with control group after treatment with TLR3 agonist at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). A significant decreasing trend was also detected in levels of IL-10 and IL-4 after treatment with TLR3 agonist compared with control group at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). Overall, this study suggested that TLR3-targeted therapies might be effective on worm burden reduction by regulation of the cytokine levels in the mice infected with T. spiralis.

• Cytokine
• TLR agonist
• Toll-like receptor
• Trichinella spiralis

• epidermal growth factor receptor
• expression
• host defense peptides
• sodium butyrate
• toll-like receptor 2

• Animals
• Butyric Acid/pharmacology
• Epithelial Cells/drug effects
• Epithelial Cells/metabolism
• ErbB Receptors/genetics
• ErbB Receptors/metabolism
• Gene Expression Regulation/drug effects
• Histone Deacetylase Inhibitors/pharmacology
• Histone Deacetylases/genetics
• Histone Deacetylases/metabolism
• Interleukin-18/genetics
• Interleukin-18/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Swine
• Toll-Like Receptor 2/genetics
• Toll-Like Receptor 2/metabolism
• beta-Defensins/genetics
• beta-Defensins/metabolism

• Citri Reticulatae Pericarpium
• gut microbiota
• metabolites
• network pharmacology
• spleen deficiency

• Scientific Research Fund of Hebei Health and Family Planning Commission

• Toll-like receptors
• intestinal bacteria
• intestinal mucosal barrier
• mice
• obstructive jaundice

Host defense peptides (HDPs) possess direct antibacterial, antineoplastic, and immunomodulatory abilities, playing a vital role in innate immunity. Dietary-regulated HDP holds immense potential as a novel pathway for preventing infection.

In this study, we examined the regulation mechanism of HDPs (pEP2C, pBD-1, and pBD-3) and cytokines (IL-8 and IL-18) expression by sodium phenylbutyrate (PBA).

The effects of PBA on HDP induction and the mechanism involved were studied in porcine intestinal epithelial cell lines (IPEC J2).

In this study, the results showed that HDPs (pEP2C, pBD-1, and pBD-3) and cytokines (IL-8 and IL-18) expression was increased significantly upon stimulation with PBA in IPEC J2 cells. Furthermore, toll-like receptor 2 (TLR2) and TLR4 were required for the PBA-mediated upregulation of the HDPs. This process occurred and further activated the NF-κB pathway via the phosphorylation of p65 and an IκB α synthesis delay. Meanwhile, histone deacetylase (HDAC) inhibition and an increased phosphorylation of histone H3 on serine S10 also occurred in PBA-induced HDP expression independently with TLR2 and TLR4. Furthermore, p38-MAPK suppressed PBA-induced pEP2C, pBD-1 pBD-3, IL-8, and IL-18 expression, but ERK1/2 failed to abolish the regulation of pBD-3, IL-8, and IL-18. Moreover, epidermal growth factor receptor (EGFR) is involved in PBA-mediated HDP regulation.

We concluded that PBA induced HDP and cytokine increases but did not cause an excessive pro-inflammatory response, which proceeded through the TLR2 and TLR4-NF-κB pathway and histone modification in IPEC J2 cells.

• b-defensins
• inflammatory cytokines
• signaling pathway
• sodium phenylbutyrate

The gut microbiome and its role in health and disease have recently been major focus areas of research. In this review, we summarize the different ways in which the gut microbiome interacts with the rest of the body, with focus areas on its relationships with immunity, the brain, and injury. The gut–brain axis, a communication network linking together the central and enteric nervous systems, represents a key bidirectional pathway with feed-forward and feedback mechanisms. The gut microbiota has a central role in this pathway and is significantly altered following injury, leading to a pro-inflammatory state within the central nervous system (CNS). Herein, we examine traumatic brain injury (TBI) in relation to this axis and explore potential interventions, which may serve as targets for improving clinical outcomes and preventing secondary brain injury.

• Traumatic brain injury (TBI)
• brain-gut axis
• central nervous system (CNS)
• commensals
• enteric nervous system (ENS)
• gastrointestinal (GI)
• gut
• microbiome

Safe and efficacious orally-delivered mucosal vaccine platforms are desperately needed to combat the plethora of mucosally transmitted pathogens. Lactobacillus spp. have emerged as attractive candidates to meet this need and are known to activate the host innate immune response in a species- and strain-specific manner. For selected bacterial isolates and mutants, we investigated the role of key innate immune pathways required for induction of innate and subsequent adaptive immune responses. Co-culture of murine macrophages with L. gasseri (strain NCK1785), L. acidophilus (strain NCFM), or NCFM-derived mutants—NCK2025 and NCK2031—elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins. Through the use of macrophage genetic knockouts, we identified Toll-like receptor 2 (TLR2), the cytosolic nucleotide-binding oligomerization domain containing 2 (NOD2) receptor, and the inflammasome-associated caspase-1 as contributors to macrophage activation, with NOD2 cooperating with caspase-1 to induce inflammasome derived interleukin (IL)-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine platform with surface expression of human immunodeficiency virus type 1 (HIV-1) Gag or membrane proximal external region (MPER), we demonstrated that NOD2 signaling is required for antigen-specific mucosal and systemic humoral responses. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a Lactobacillus acidophilus mucosal vaccine platform.

• Administration, Oral
• Animals
• Antigens/administration & dosage
• Caspase 1/genetics
• Caspase 1/immunology
• Genes, gag/genetics
• HIV-1/immunology
• HIV-1/pathogenicity
• Humans
• Immunity, Humoral/genetics
• Immunity, Humoral/immunology
• Inflammasomes/genetics
• Inflammasomes/immunology
• Interleukin-1beta/genetics
• Interleukin-1beta/immunology
• Lactobacillus acidophilus/immunology
• Lipopolysaccharides/immunology
• Lipopolysaccharides/metabolism
• Macrophages/immunology
• Macrophages/microbiology
• Mice
• Nod2 Signaling Adaptor Protein/genetics
• Nod2 Signaling Adaptor Protein/immunology
• Teichoic Acids/immunology
• Teichoic Acids/metabolism
• Toll-Like Receptor 2/genetics
• Toll-Like Receptor 2/immunology
• Vaccines/administration & dosage
• Vaccines/immunology

• R01 DE019069 NIDCR NIH HHS
• R21 AI112486 NIAID NIH HHS
• R01 DE019069 NIH HHS
• R21 AI112486 NIH HHS
• National Institutes of Health

• Primary antibody deficiency
• adaptive and innate immune deficiencies
• bronchiectasis
• respiratory tract infection
• treatment and disease progression

• Anti-Bacterial Agents/therapeutic use
• Bacterial Infections/immunology
• Bacterial Infections/pathology
• Bronchiectasis/immunology
• Bronchiectasis/pathology
• Chronic Disease
• Common Variable Immunodeficiency/diagnosis
• Common Variable Immunodeficiency/pathology
• Complement System Proteins/immunology
• Disease Progression
• Humans
• Immunologic Factors/immunology
• Lung Diseases, Interstitial/immunology
• Lung Diseases, Interstitial/pathology
• Neutrophils/immunology
• Respiratory Tract Infections/immunology
• Respiratory Tract Infections/microbiology
• Respiratory Tract Infections/pathology
• T-Lymphocytes/immunology
• Virus Diseases/immunology
• Virus Diseases/pathology

TLR4 in intestinal epithelial cells has been shown both inflammatory and homeostatic roles following binding of its cognate ligand lipopolysaccharide (LPS). TWEAK-Fn14 axis plays an important role in pathologies caused by excessive or abnormal inflammatory responses. This study aimed to evaluate potential cross-talk between TLR4 and TWEAK/Fn14 system in porcine small intestinal epithelial cells. Our in vivo results showed that, compared with the age-matched normal control piglets, increased expression of Fn14 in epithelium and decreased TWEAK expression in lamina propria were detected in the small intestinal of piglets stimulated with LPS. Consistent with this finding, treatment with LPS increased the expression of Fn14 and TLR4 while decreased TWEAK expression in porcine small intestinal epithelial cell lines SIEC02. Interestingly, modulating Fn14 activation using agonistic anti-Fn14 decreased TLR4-mediated TNF-α production by SIEC02. In addition, pretreatment of LPS-stimulated SIEC02 with recombinant TWEAK protein suppresses the expression of Fn14 and TNF-α and inhibits the negative impact of LPS on the tight junctional protein occludin expression. In conclusion, this study demonstrates that the TWEAK-independent Fn14 activation augments TLR4-mediated inflammatory responses in the intestine of piglets. Furthermore, the TWEAK-dependent suppression of Fn14 signaling may play a role in intestinal homeostasis.

• Fn14
• TLR4
• TNF-α
• TWAEK
• lipopolysaccharide
• small intestinal epithelial cells

• tlr1
• chemo-efficacy
• metastatic colorectal cancer

• Aged
• Aged, 80 and over
• Alleles
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bevacizumab/administration & dosage
• Camptothecin/analogs & derivatives
• Camptothecin/therapeutic use
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Female
• Fluorouracil/therapeutic use
• Genes, ras
• Genotype
• Humans
• Leucovorin/therapeutic use
• Male
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Retreatment
• Toll-Like Receptor 1/genetics
• Treatment Outcome

• R01 CA166161 NCI NIH HHS
• R21 CA182595 NCI NIH HHS
• P30 CA014089 NCI NIH HHS
• R01 DK104908 NIDDK NIH HHS
• U10 CA180830 NCI NIH HHS

• CCl(4)-induced hepatotoxicity
• Ginsenoside Rg1
• Inflammation

• Animals
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/therapeutic use
• Carbon Tetrachloride Poisoning/drug therapy
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/physiopathology
• China
• Ginsenosides/pharmacology
• Ginsenosides/therapeutic use
• Inflammation/drug therapy
• Inflammation/etiology
• Inflammation/metabolism
• Liver/drug effects
• Male
• Mice
• Protective Agents/pharmacology

• gut
• immune tolerance
• microbiota
• pattern recognition receptors
• symbiosis

• Host-probiotic interaction
• Polyphosphate
• Probiotics

• Adaptive Immunity
• Autoimmunity
• Inflammation
• Innate Immunity
• Receptors, Pattern Recognition

• Animals
• Bacteria/immunology
• Evolution, Molecular
• Female
• Graft Rejection/immunology
• Graft Rejection/metabolism
• Graft Rejection/prevention & control
• Graft Survival
• Host-Pathogen Interactions
• Humans
• Immunity, Innate
• Immunity, Mucosal
• Intestines/immunology
• Intestines/microbiology
• Models, Immunological
• Organ Transplantation/adverse effects
• Placenta/immunology
• Pregnancy
• Signal Transduction
• Transplantation Tolerance
• Treatment Outcome

• Crohn’s disease
• adverse events
• inflammatory bowel disease
• infliximab
• monoclonal antibodies
• safety
• treatment
• ulcerative colitis

• AICAR
• AMP-activated protein kinase
• Carbon tetrachloride
• Hepatitis
• Inflammation

• Bacteria, Anaerobic/physiology
• Epithelial Cells/microbiology
• Homeostasis
• Humans
• Immune System/microbiology
• Inflammatory Bowel Diseases/microbiology
• Intestine, Large/immunology
• Intestine, Large/microbiology
• Microbiota
• Symbiosis

Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10¹⁴ organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

• Animal models
• Gut microbiota
• Diabetes
• Obesity
• Cancer
• Allergy
• Behavior
• Colitis

• Animals
• Bacteria/classification
• Bacteria/growth & development
• Bacteria/immunology
• Disease Models, Animal
• Gastrointestinal Diseases/immunology
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/microbiology
• Host-Pathogen Interactions
• Humans
• Mice
• Microbiota
• Rats
• Species Specificity
• Specific Pathogen-Free Organisms