• colonization resistance
• enteric infections
• gut homeostasis
• microbiota
• mucosal immunity

• Microbiota byproducts
• central trained immunity
• inflammation
• phenolic derivatives

• Phloroglucinol/pharmacology
• Phloroglucinol/metabolism
• Animals
• Gastrointestinal Microbiome/drug effects
• Mice
• Receptors, Aryl Hydrocarbon/metabolism
• Mice, Inbred C57BL
• Inflammation/metabolism
• Inflammation/prevention & control
• Macrophages/drug effects
• Macrophages/immunology
• Macrophages/metabolism
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/metabolism
• Immunity, Innate/drug effects
• Anti-Inflammatory Agents/pharmacology
• Disease Models, Animal
• Basic Helix-Loop-Helix Transcription Factors/metabolism
• Basic Helix-Loop-Helix Transcription Factors/genetics

• clinical microbiology
• microbiota

• Humans
• Animals
• Mice
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/microbiology
• RNA, Ribosomal, 16S/genetics
• Colitis
• Inflammatory Bowel Diseases
• Immunoglobulin A
• Mitochondria/genetics
• Disease Progression

• UL1 TR001863 NCATS NIH HHS
• Eusko Jaurlaritza (Basque Government)
• Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)

• dextran sulfate sodium
• gut microbiota
• inflammatory bowel disease
• intestinal inflammation
• peptides

• Mice
• Animals
• Gastrointestinal Microbiome
• Dysbiosis/chemically induced
• Dysbiosis/drug therapy
• Colitis/chemically induced
• Colitis/drug therapy
• Inflammatory Bowel Diseases/pathology
• Cytokines/metabolism
• Inflammation/pathology
• Dextran Sulfate/adverse effects
• Mice, Inbred C57BL
• Disease Models, Animal
• Colon/metabolism

• 31600614, 82072953 National Nature Science. China

• biological clock
• circadian rhythm
• clock genes
• inflammatory bowel disease
• intestinal diseases

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγt^high-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

• Daikenchuto (DKT)
• Japanese herbal medicine (Kampo medicine)
• Lactobacillaceae
• biomolecular functions of herbal medicine
• colonic homeostasis
• experimental colitis
• group 3 innate lymphoid cells (ILC3s)
• gut microbiota

• Alginate
• Microspheres
• colon-targeted delivery system

• colonization resistance
• commensals
• enteric infections
• gut microbiota
• microbial interaction
• pathogens

• Animals
• Bacteria
• Bacterial Infections
• Gastrointestinal Microbiome
• Virulence

• Brain regions
• Complex I deficiency
• Leigh syndrome
• Metabolomics
• Mitochondrial disease
• Ndufs4 knockout mice

• Animals
• Electron Transport Complex I/metabolism
• Leigh Disease/metabolism
• Metabolome
• Metabolomics
• Mice
• Mice, Knockout

• IBD
• dog
• epithelial barrier
• intestinal permeability
• microbiota
• mouse

• R01 GM099537 NIGMS NIH HHS

• Autophagy
• cytokines
• inflammation
• macrophages
• microbiota

• Crohn's disease
• gasdermin E
• intestinal epithelial cell
• pyroptosis

• Animals
• Colitis/chemically induced
• Colitis/immunology
• Colitis/metabolism
• Colitis/pathology
• Crohn Disease/pathology
• Epithelial Cells/metabolism
• Epithelial Cells/pathology
• HMGB1 Protein/metabolism
• Hematopoiesis
• Humans
• Inflammation/pathology
• Intestinal Mucosa/pathology
• Intestines/pathology
• Male
• Mice, Inbred C57BL
• Pore Forming Cytotoxic Proteins/deficiency
• Pore Forming Cytotoxic Proteins/metabolism
• Pyroptosis
• Severity of Illness Index
• Trinitrobenzenesulfonic Acid
• Mice

• exhaust air dust PCR
• health monitoring
• hygienic standardization
• metagenomic analysis
• microbiological diagnostics
• microbiome analysis
• research validity
• rodent pathogens

• DSS-induced colitis development
• dynamics
• gut microbes
• intestinal microbiota
• longitudinal studies
• susceptibility

• NRF-2017R1D1A1B03032587. National Research Foundation of Korea

• Fecal microbiota transplantation
• antibiotics
• experimental design
• germ-free
• gnotobiotic
• human
• methods
• microbiota depletion
• rodent

• Animal Experimentation/standards
• Animals
• Disease Models, Animal
• Fecal Microbiota Transplantation/standards
• Feces/microbiology
• Gastrointestinal Microbiome
• Germ-Free Life
• Guidelines as Topic
• Humans
• Rodentia/microbiology

Atopic dermatitis is a chronic eczema commonly observed among children in Western countries. The gut microbiota is a significant factor in the pathogenesis, and ways to promote intestinal colonizers with anti-inflammatory capabilities are therefore favorable. The present study addressed the effects of a prebiotic, xylooligosaccharide (XOS), on the gut microbiota and ear inflammation in an oxazolone-induced dermatitis model in BALB/c mice. Mice were fed a XOS supplemented or a control diet throughout the experiment. Ear thickness and clinical skin inflammation were scored blindly after three weeks topical challenge with 0.4% oxazolone. The mice were divided into high and low responders to oxazolone-induced dermatitis based on clinical inflammation and histological evaluation of ear biopsies, and significantly fewer high responders were present in the XOS fed group. In addition, XOS fed mice had higher abundance of Prevotella spp. in their gut microbiota compared to the control fed mice. Serum IgE and ear tissue cytokine levels correlated significantly with the clinical scores, and with the abundance of Prevotella spp. The strong association between the low-responding phenotype and high abundance of Prevotella spp., indicates an alleviating effect of this intestinal colonizer in allergic sensitization. Prevotella should be considered as a relevant target for future microbiota-directed treatment strategies in atopic patients.

• Cohousing
• ConA hepatitis
• Coprophagy

• IBD
• TNF
• gut microbes
• immune responses
• immunotherapy

Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.

• disease model
• ethics and welfare
• microorganism
• organisms and models
• quality assurance/control

• Bacteriophages
• animal model reproducibility
• gut microbiota
• vendor effect
• virome

• Animals
• Bacteria/classification
• Bacteria/genetics
• Bacteria/virology
• Bacterial Physiological Phenomena
• Bacteriophages/classification
• Bacteriophages/genetics
• DNA, Bacterial/analysis
• DNA, Viral/analysis
• Diet
• Diet, High-Fat/adverse effects
• Feces/microbiology
• Gastrointestinal Microbiome/genetics
• Gastrointestinal Microbiome/physiology
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• RNA, Ribosomal, 16S/genetics
• Reproducibility of Results
• Sequence Analysis, DNA
• Virus Physiological Phenomena

• 16S rRNA gene sequencing
• Antibiotics
• Gut barrier permeability
• Gut-brain axis
• Inbred strain

Various environmental contaminants including heavy metals, pesticides and antibiotics can contaminate food and water, leading to adverse effects on human health, such as inflammation, oxidative stress and intestinal disorder. Therefore, remediation of the toxicity of foodborne contaminants in human has become a primary concern. Some probiotic bacteria, mainly Lactobacilli, have received a great attention due to their ability to reduce the toxicity of several contaminants. For instance, Lactobacilli can reduce the accumulation and toxicity of selective heavy metals and pesticides in animal tissues by inhibiting intestinal absorption of contaminants and enhancing intestinal barrier function. Probiotics have also shown to decrease the risk of antibiotic-associated diarrhea possibly via competing and producing antagonistic compounds against pathogenic bacteria. Furthermore, probiotics can improve immune function by enhancing the gut microbiota mediated anti-inflammation. Thus, these probiotic bacteria are promising candidates for protecting body against foodborne contaminants-induced toxicity. Study on the mechanism of these beneficial bacterial strains during remediation processes and particularly their interaction with host gut microbiota is an active field of research. This review summarizes the current understanding of the remediation mechanisms of some probiotics and the combined effects of probiotics and gut microbiota on remediation of foodborne contaminants in vivo.

• environmental contaminants
• foodborne
• gut microbiota
• probiotics
• remediation

• Animals
• Anti-Bacterial Agents/adverse effects
• Diarrhea/chemically induced
• Diarrhea/prevention & control
• Environmental Pollutants/toxicity
• Food Contamination
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/immunology
• Gastrointestinal Microbiome/physiology
• Humans
• Metals, Heavy/toxicity
• Pesticides/toxicity
• Probiotics/administration & dosage
• Probiotics/pharmacology

• Colitis
• bacterial internalization
• barrier function
• colorectal cancers
• epithelial permeability
• intestinal dysbiosis

• caspase-11
• colitis
• microbiota
• dss
• il-10

Gut microbiota help to educate the immune system and a number of involved immune cells were recently characterized. However, specific molecular determinants in these processes are not known, and, reciprocally, little information exists about single host determinants that alter the microbiota. Gelatinase B/matrix metalloproteinase-9 (MMP-9), an innate immune regulator and effector, has been suggested as such a host determinant. In this study, acute colitis was induced in co-housed MMP-9^-/- mice (n = 10) and their wild-type (WT) littermates (n = 10) via oral administration of 3% dextran sodium sulfate (DSS) for 7 days followed by 2 days of regular drinking water. Control mice (10 WT and 10 MMP-9^-/-) received normal drinking water. Fecal samples were collected at time of sacrifice and immediately frozen at −80 °C. Microbiota analysis was performed using 16S rRNA amplicon sequencing on Illumina MiSeq and taxonomic annotation was performed using the Ribosomal Database Project as reference. Statistical analysis correcting for multiple testing was done using R. No significant differences in clinical or histopathological parameters were found between both genotypes with DSS-induced colitis. Observed microbial richness at genus level and microbiota composition were not significantly influenced by host genotype. In contrast, weight loss, disease activity index, cage, and phenotype did significantly influence the intestinal microbiota composition. After multivariate analysis, cage and phenotype were identified as the sole drivers of microbiota composition variability. In conclusion, changes in fecal microbiota composition were not significantly altered in MMP-9-deficient mice compared to wild-type littermates, but instead were mainly driven by DSS-induced colonic inflammation.

A protein that regulates aspects of the immune system has been proposed to influence gut microbial populations implicated in the inflammatory conditions known as colitis, but new evidence suggests the protein has no such effect. Ghislain Opdenakker and colleagues at the Rega Institute for Medical Research in Belgium examined the issue in mice with chemically induced colitis. The gut microbes of normal “wild-type” animals were compared with those in animals lacking the gene for the protein, “gelatinase B/matrix metalloproteinase-9”. The absence of the gene, and therefore of the protein it codes for, caused no significant alteration in the gut microbial population. The presence of colitis, however, did alter the gut microbial population relative to mice with no colitis. The results will assist work to understand the networks of cause and effect linking gut microbes and colitis.

• Animals
• Feces/microbiology
• Gastrointestinal Microbiome
• Germ-Free Life
• Housing, Animal
• Humans
• Mice
• Microbiota
• Phenotype
• Survival Analysis
• Thermography
• Time Factors

• P01 DK091222 NIDDK NIH HHS
• P30 DK097948 NIDDK NIH HHS
• R01 DK042191 NIDDK NIH HHS
• R56 DK055812 NIDDK NIH HHS
• R01 DK055812 NIDDK NIH HHS

Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM) is an established risk allele in CD. We have shown previously that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1^−/− mice were rederived into specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1^−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1^−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1^−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1^−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1^−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1^−/− mice as a model to elucidate host-environment interactions that regulate mucosal homeostasis and intestinal inflammatory responses. Defining such interactions will be essential for developing novel preventative and therapeutic strategies for human CD.

Summary: In this study, we rederived conventionally raised Irgm1-deficient mice into specific pathogen-free and germ-free conditions. We show that these environments determine how Irgm1 regulates Paneth cell function and gut inflammation susceptibility.

• Experimental colitis
• Immunity-related GTPases
• Inflammatory bowel diseases

• colitis
• colonization inflammation
• exercise
• germ-free
• gut
• microbiome
• microbiota
• transplant
• voluntary wheel running

• Dextran sodium sulfate
• Experimental colitis
• Inflammatory bowel disease
• Intestinal barrier
• Pathogenesis

• Animals
• Colon/metabolism
• Colon/pathology
• Cytokines/metabolism
• Dextran Sulfate/toxicity
• Disease Models, Animal
• Gastrointestinal Microbiome/immunology
• Humans
• Inflammatory Bowel Diseases/chemically induced
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/etiology
• Inflammatory Bowel Diseases/pathology
• Metabolome
• Mice
• Mucins/metabolism
• Permeability
• Probiotics/therapeutic use
• Reproducibility of Results
• Time Factors

• I01 BX001155 BLRD VA

• Bacterial Translocation/physiology
• Gastrointestinal Microbiome/physiology
• Humans
• Population Dynamics

• Wellcome Trust
• 098051 Wellcome Trust
• MR/K000551/1 Medical Research Council

• C57BL/6J inbred mice
• fecal metabolome
• fecal microbiota
• mice generations
• microbiome variation

• bile acids
• colitis
• dysbiosis

• Crohn's disease
• Inflammatory Bowel Disease
• fecal microbiota transplant
• ulcerative colitis

• Asparagus
• Colitis
• Microbiota
• Quercetin
• Rutin

• Animals
• Colitis/chemically induced
• Colon/metabolism
• Cytokines/metabolism
• Dextran Sulfate/adverse effects
• Dietary Supplements
• Disease Models, Animal
• Inflammation
• Interleukins/metabolism
• Intestinal Mucosa/drug effects
• Male
• Mice
• Mice, Inbred C57BL
• Rutin/analysis
• Rutin/pharmacology
• Sulfates/pharmacology
• Interleukin-22

• animal experimentation
• bacteria
• breeding
• experimental animal models
• microbiota
• rodentia

• gnotobiology
• humanization
• inflammation
• microbial consortia

• Gut-brain axis
• caffeine
• constipation
• dietary fiber
• gut motility
• gut permeability
• inflammation
• nicotine
• non-motor symptoms
• risk factors

• Colitis
• Dextran sulfate sodium
• Dysbiosis
• Mice
• Microbiota

The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gut microbiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gut microbiota as potential treatment for inflammatory diseases.

• Chronic granulomatous disease
• Colitis
• Dextran sodium sulfate
• Inflammatory bowel disease
• Microbiome
• NADPH
• Reactive oxygen species
• p47 phox

• Adult
• Animals
• Citrobacter rodentium/pathogenicity
• Citrobacter rodentium/physiology
• Colitis/chemically induced
• Colitis/genetics
• Colitis/microbiology
• Colitis/pathology
• Crosses, Genetic
• Dextran Sulfate
• Disease Models, Animal
• Disease Susceptibility
• Female
• Gene Expression
• Granulomatous Disease, Chronic/genetics
• Granulomatous Disease, Chronic/microbiology
• Granulomatous Disease, Chronic/pathology
• Humans
• Inflammatory Bowel Diseases/chemically induced
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/pathology
• Mice
• Mice, Knockout
• Microbiota/genetics
• NADP/metabolism
• NADPH Oxidases/deficiency
• NADPH Oxidases/genetics
• Reactive Oxygen Species/metabolism

• Wellcome Trust
• HHSN261200800001C NCI NIH HHS
• HHSN261200800001E NCI NIH HHS
• Intramural NIH HHS
• Division of Intramural Research, National Institute of Allergy and Infectious Diseases