• Intestinal microbiota
• advanced analysis techniques
• inflammatory bowel disease
• microbiome-based diagnostic
• personalized therapy

• Humans
• Gastrointestinal Microbiome
• Precision Medicine
• Animals
• Fecal Microbiota Transplantation
• Colitis, Ulcerative/therapy
• Colitis, Ulcerative/microbiology
• Colitis, Ulcerative/diagnosis
• Inflammatory Bowel Diseases/therapy
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/diagnosis
• Crohn Disease/therapy
• Crohn Disease/microbiology
• Crohn Disease/diagnosis

• Holstein
• Xinjiang Brown
• breed
• feces
• microbiota
• rumen

• 2022YFE0115700 National Key Research and Development Projects
• CARS-36 China Agriculture Research System of MOF and MARA
• IRT_15R62 program for the Changjiang Scholar and Innovation Research Team

• gut microbiota
• holobiont
• host–microbe interaction

• Animals
• Gastrointestinal Microbiome
• Microbiota
• Host Microbial Interactions
• Metagenomics

• European Union – NextGenerationEU
• European Union

• Humans
• Animals
• Female
• Male
• Mice
• RNA, Ribosomal, 16S/genetics
• Microbiota
• Gastrointestinal Microbiome
• Feces/microbiology
• Ileum
• Bacteria/genetics

• F31 HD105403 NICHD NIH HHS
• R01 HD095412 NICHD NIH HHS
• Eunice Kennedy Shriver National Institute of Child Health and Human Development

• LPS
• TLR4/NF-κB signaling pathway
• colonic mucosal injury
• hypoxia

• Asian sea bass
• cytokine
• digesta
• gut microbiota
• mucosa
• salinity

• Ministry of Education

A wide range of microbial pathogens can enter the gastrointestinal tract, causing mucosal inflammation and infectious colitis and accounting for most cases of acute diarrhea. Severe cases of infectious colitis can persist for weeks, and if untreated, may lead to major complications and death. While the molecular pathogenesis of microbial infections is often well-characterized, host-associated epithelial factors that affect risk and severity of infectious colitis are less well-understood. The current study characterized functions of the zinc (Zn) transporter ZnT2 (SLC30A2) in cultured HT29 colonocytes and determined consequences of ZnT2 deletion in mice on the colonic response to enteric infection with Citrobacter rodentium. ZnT2 in colonocytes transported Zn into vesicles buffering cytoplasmic Zn pools, which was important for Toll-like receptor 4 (TLR4) expression, activation of pathogen-stimulated NF-κβ translocation and cytokine expression. Additionally, ZnT2 was critical for lysosome biogenesis and bacterial-induced autophagy, both promoting robust host defense and resolution mechanisms in response to enteric pathogens. These findings reveal that ZnT2 is a novel regulator of mucosal inflammation in colonocytes and is critical to the response to infectious colitis, suggesting that manipulating the function of ZnT2 may offer new therapeutic strategies to treat specific intestinal infections.

• Animals
• Cation Transport Proteins/genetics
• Cation Transport Proteins/metabolism
• Colitis/etiology
• Colitis/genetics
• Colitis/metabolism
• Cytokines/genetics
• Cytokines/metabolism
• HT29 Cells
• Humans
• Inflammation/genetics
• Inflammation/metabolism
• Intestinal Mucosa/metabolism
• Mice
• Mice, Inbred C57BL
• Toll-Like Receptor 4/genetics
• Toll-Like Receptor 4/metabolism
• Zinc/metabolism

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Furthermore, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. Several mucosa-associated bacterial taxa have high heritability estimates, and interestingly, 16S rRNA transcript-based heritability estimates are positively correlated with cospeciation rate estimates. Genome-wide association mapping identifies 428 loci influencing 120 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.

The digestive system, particularly the large intestine, hosts many types of bacteria which together form the gut microbiome. The exact makeup of different bacterial species is specific to an individual, but microbiomes are often more similar between related individuals, and more generally, across related species. Whether this is because individuals share similar environments or similar genetic backgrounds remains unclear. These two factors can be disentangled by breeding different animal lineages – which have different genetic backgrounds while belonging to the same species – and then raising the progeny in the same environment.

To investigate this question, Doms et al. studied the genes and microbiomes of mice resulting from breeding strains from multiple locations in a natural hybrid zone between different subspecies. The experiments showed that 428 genetic regions affected the makeup of the microbiome, many of which were known to be associated with human diseases. Further analysis revealed 79 genes that were particularly interesting, as they were involved in recognition and communication with bacteria. These results show how the influence of the host genome on microbiome composition becomes more specialized as animals evolve.

Overall, the work by Doms et al. helps to pinpoint the genes that impact the microbiome; this knowledge could be helpful to examine how these interactions contribute to the emergence of conditions such as diabetes or inflammatory bowel disease, which are linked to perturbations in gut bacteria.

• GWAS
• codiversification
• cospeciation
• evolutionary biology
• genetics
• genomics
• hybridization
• microbiome
• mouse
• phylosymbiosis

• TFF3
• colitis
• esophagus
• gut bacteria
• gut microbiome
• intestine
• microbiota
• mucus
• stomach
• trefoil factor

• Animals
• Bacteria/isolation & purification
• DNA Barcoding, Taxonomic
• Gastrointestinal Tract/microbiology
• High-Throughput Nucleotide Sequencing
• Male
• Mice
• Microbiota

• European Commission through the "European Funds for Regional Development" (EFRE)
• Ministry of Economy, Science and Digitalization of Saxony-Anhalt: research program "Autonomy in Old Age" ("LiLife" project ID: ZS/2018/11/95324)

• Animals
• Anti-Bacterial Agents/metabolism
• Epithelial Cells/metabolism
• Gene Expression Regulation/physiology
• Inflammation/metabolism
• Intestinal Mucosa/metabolism
• Intestines/metabolism
• Macrophages/drug effects
• Mice
• Mice, Inbred C57BL
• NF-kappa B/metabolism
• Signal Transduction/physiology
• Tumor Necrosis Factors/metabolism

• 323040 European Research Council
• SNF 179490 Swiss National Science Foundation
• 310030_53074 Swiss National Science Foundation
• ETH Zurich
• Swedish Research Council
• Swedish Foundation for Strategic Research

• Colitis
• Gut microbiota
• Intestinal barrier
• Pinocembrin
• TLR4/MD2/NF-κB

• CpG sites
• Immune response
• LPS
• Phenotypic plasticity
• Toll-like receptors

• Calve
• Feeding
• Gastrointestinal tract
• Host health
• Immune system
• Microbiome

The gut microbiota plays multiple critical roles in maintaining the health of the host, especially in ruminants. However, our understanding of the establishment of gut microbiota from birth to adulthood is still limited. To address this, the bacterial ecology of the rumen, abomasum, duodenum, and rectum in Holstein cows ranging in age from 1 week to 5 years old was investigated using 16S rRNA gene sequencing in this study. A major change in the composition, diversity, and abundance of bacteria was observed with increased age (p < 0.05). Microbiota gradually matured in each gut segment and followed the Gompertz model when the Chao1, Shannon, and maturity indexes (p < 0.05, r > 0.94) were applied. Importantly, the Gompertz model parameter differed between the gut segments, with the highest microbiota growth rate found in the rectum, followed by the rumen, abomasum, and duodenum. Compared to older animals, greater microbiota similarities were found in the adjacent gut segments of younger animals (p < 0.05). Our findings indicate that gut microbiotas are established quickly when cows are young and then slow with age and that early in life, hindgut microbiota may be more easily affected by the foregut microbiota.

• bacterial ecology
• cows
• maturity
• microbiota establishment

• Biogeography
• Community assembly
• Composition
• Gut
• Human microbiome
• Regional
• Respiratory tract
• Skin
• Vagina

Many studies have investigated the anti-obesity effects of probiotics in animal models and humans. However, few studies have focused on the mechanisms of obesity-inducing probiotics. In a previous study, we demonstrated that specific bacterial strains isolated from kefir, Lactobacillus kefirnofaciens M1 and Lactobacillus mali APS1, possess obesity and anti-obesity effects, respectively, in high-fat diet (HFD)-induced obese mice. Thus, in the present study, we systematically investigated whether APS1 and M1 affect energy homeostasis and lipid metabolism in HFD-induced obese mice and how this might be achieved. We observed that the M1/APS1 intervention influenced fat accumulation by regulating adipogenesis and inflammation-related marker expression both in vitro and in a HFD induced C57BL/6J mice model. We also observed putative links between key taxa and possible metabolic processes of the gut microbiota. Notably, families Christensenellaceae and S24_7 were negatively correlated with body weight gain through increase in the essential esterized carnitine for energy expenditure. These results suggest the importance of specific probiotic interventions affecting leanness and obesity of subjects under a HFD, which are operated by modulating the tripartite relationship among the host, microbiota, and metabolites.

• Lactobacillus kefiranofaciens M1
• Lactobacillus mali APS1
• metabolomics
• microbolomics
• obesity

• IL-17
• TLRs
• antibiotics
• antifungal immune regulation
• gut microbiota

• APN
• PDCoV
• enteroids
• interferon
• interferon receptor

• Firmicutes
• IL-4
• Lactobacillus species
• TiO2 nanoparticles
• gastrointestinal tract
• mucin-2
• segmented filamentous bacteria
• weight gain

• Air pollution
• Intestinal microbiome
• Intestinal redox lipidome

• Air Pollutants/toxicity
• Air Pollution/adverse effects
• Air Pollution/analysis
• Lipidomics
• Microbiota
• Oxidation-Reduction
• Particulate Matter/toxicity

• R01 ES029395 NIEHS NIH HHS

• Cancer Biogeography
• Colorectal Carcinogenesis
• FFQ
• Fecal Microbes

• Aged
• Bacteria/isolation & purification
• Bacteria/metabolism
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/prevention & control
• Diet Surveys/statistics & numerical data
• Feces/microbiology
• Feeding Behavior/physiology
• Follow-Up Studies
• Gastrointestinal Microbiome/physiology
• Health Personnel/statistics & numerical data
• Humans
• Incidence
• Male
• Massachusetts/epidemiology
• Middle Aged
• Prospective Studies
• Risk Factors
• Sulfur/metabolism

• C10674/A27140 Cancer Research UK
• 27140 Cancer Research UK
• P30 DK043351 NIDDK NIH HHS
• U01 CA152904 NCI NIH HHS
• K24 DK098311 NIDDK NIH HHS
• K07 CA218377 NCI NIH HHS
• R00 CA215314 NCI NIH HHS
• K01 DK120742 NIDDK NIH HHS
• L30 DK118604 NIDDK NIH HHS
• K99 DK119412 NIDDK NIH HHS
• R35 CA197735 NCI NIH HHS
• K01 DK110267 NIDDK NIH HHS
• R01 CA202704 NCI NIH HHS
• P01 CA055075 NCI NIH HHS
• R01 CA151993 NCI NIH HHS
• U01 CA167552 NCI NIH HHS
• L30 CA209764 NCI NIH HHS
• K23 DK125838 NIDDK NIH HHS
• U54 DE023798 NIDCR NIH HHS
• T32 CA009001 NCI NIH HHS
• UM1 CA167552 NCI NIH HHS

A complex microbiota inhabits various microenvironments of the gut, with some symbiotic bacteria having evolved traits to invade the epithelial mucus layer and reside deep within intestinal tissue of animals. Whether these distinct bacterial communities across gut biogeographies exhibit divergent behaviors remains largely unknown. Global transcriptomic analysis to investigate microbial physiology in specific mucosal niches has been hampered technically by overabundance of host RNA. Herein, we employed hybrid selection RNA sequencing (hsRNA-Seq) to enable detailed spatial transcriptomic profiling of a prominent human commensal as it colonizes the colonic lumen, mucus or epithelial tissue of mice. Compared to conventional RNA-Seq, hsRNA-Seq increased reads mapping to the Bacteroides fragilis genome by 48- and 154-fold in mucus and tissue, respectively, allowing for high fidelity comparisons across biogeographic sites. Near the epithelium, B. fragilis up-regulated numerous genes involved in protein synthesis, indicating that bacteria inhabiting the mucosal niche are metabolically active. Further, a specific sulfatase (BF3086) and glycosyl hydrolase (BF3134) were highly induced in mucus and tissue compared to bacteria in the lumen. In-frame deletion of these genes impaired in vitro growth on mucus as a carbon source, as well as mucosal colonization of mice. Mutants in either B. fragilis gene displayed a fitness defect in competing for colonization against bacterial challenge, revealing the importance of site-specific gene expression for robust host-microbial symbiosis. As a versatile tool, hsRNA-Seq can be deployed to explore the in vivo spatial physiology of numerous bacterial pathogens or commensals.

• bacteria
• chronic inflammatory enteropathy
• colon
• dogs
• fluorescence in situ hybridization
• inflammatory bowel disease
• microbiome
• microbiota

Crohn’s Disease and Ulcerative Colitis are chronic, inflammatory conditions of the digestive tract, collectively known as Inflammatory Bowel Disease (IBD). The combined influence of lifestyle factors, genetics, and the gut microbiome contribute to IBD pathogenesis. Studies of the gut microbiome have shown significant differences in its composition between healthy individuals and those with IBD. Due to the high inter-individual microbiome variation seen in humans, mouse models of IBD are often used to investigate potential IBD mechanisms and their interplay between host, microbial, and environmental factors. While fecal samples are the predominant material used for microbial community analysis, they may not be the ideal sample to use for analysis of the microbiome of mice with experimental colitis, such as that induced by 2, 4, 6 trinitrobenzesulfonic acid (TNBS). As TNBS is administered intrarectally to induce colitis and inflammation is confined to the colon in this model, we hypothesized that the microbiome of the colonic mucus would most closely correlate with TNBS colitis severity. Based on our previous research, we also hypothesized that sex would be associated with both disease severity and microbial differences in mice with chronic TNBS colitis. We examined and compared the fecal, cecal content, and colonic mucus microbiota of 8-week old male and female C57BL/6J wild-type mice prior to and after the induction of TNBS colitis via 16S rRNA gene sequencing. We found that the colonic mucus microbiome was more closely correlated with disease severity than were alterations in the fecal and cecal microbiomes. We also found that the microbiomes of the feces, cecum, and mucus were distinct, but found no significant differences that were associated with sex in either compartment. Our findings highlight the importance of sampling colonic mucus in TNBS-induced colitis. Moreover, consideration of the differential impact of sex on the microbiome across mouse strains may be critical for the appropriate application of TNBS colitis models and robust comparisons across studies in the future.

• H2S
• Toll-like receptors
• intestinal motility
• microbiota

The kynurenine pathway is important in cellular energy generation and limiting cellular ageing as it degrades about 90% of dietary tryptophan into the essential co-factor NAD⁺ (nicotinamide adenine dinucleotide). Prior to the production of NAD⁺, various intermediate compounds with neuroactivity (kynurenic acid, quinolinic acid) or antioxidant activity (3-hydroxykynurenine, picolinic acid) are synthesized. The kynurenine metabolites can participate in numerous neurodegenerative disorders (Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease) or other diseases such as AIDS, cancer, cardiovascular diseases, inflammation, and irritable bowel syndrome. Recently, the role of gut in affecting the emotional and cognitive centres of the brain has attracted a great deal of attention. In this review, we focus on the bidirectional communication between the gut and the brain, known as the gut-brain axis. The interaction of components of this axis, namely, the gut, its microbiota, and gut pathogens; tryptophan; the kynurenine pathway on tryptophan availability; the regulation of kynurenine metabolite concentration; and diversity and population of gut microbiota, has been considered.

• gut microbiota
• gut-brain axis
• indoleamine 2,3-dioxygenase
• kynurenine pathway
• neurodegenerative disorder
• tryptophan

The role of microbiota in Crohn’s disease (CD) is increasingly recognized. However, most of the reports are from Western populations. Considering the possible variation from other populations, the aim of this study was to describe the microbiota profile in children with CD in Saudi Arabia, a non-Western developing country population.

Significantly more abundant genera in children with CD included Fusobacterium, Peptostreptococcus, Psychrobacter, and Acinetobacter; whereas the most significantly-depleted genera included Roseburia, Clostridium, Ruminococcus, Ruminoclostridium, Intestinibacter, Mitsuokella, Megasphaera, Streptococcus, Lactobacillus, Turicibacter, and Paludibacter. Alpha diversity was significantly reduced in stool (p = 0.03) but not in mucosa (p = 0.31). Beta diversity showed significant difference in community composition between control and CD samples (p = 0.03).

In this developing country, we found a pattern of microbiota in children with CD similar to Western literature, suggesting a role of recent dietary lifestyle changes in this population on microbiota structure.

• Bacteriome
• Inflammatory bowel disease
• Saudi children

Gut microbiota contributes to intestinal and immune homeostasis through host-microbiota interactions. Distribution of the gut microbiota differs according to the location in the gastrointestinal tract. Although the microbiota properties change with age, evidence for the regional difference of gut microbiota has been restricted to the young. The aim of this study is to compare the gut microbiota between terminal ileum and cecum of old rats.

We analyzed gut microbiome of luminal contents from ileum and cecum of 74-week-old and 2-year-old rats (corresponding to 60-year and 80-year-old of human age) by metagenome sequencing of 16S rRNA.

Inter-individual variation (beta diversity) of microbiota was higher in ileum than in cecum. Conversely, alpha diversity of microbiota composition was higher in cecum than in ileum. Lactobacillaceae were more abundant in ileum compared to cecum while Ruminococcaceae and Lachnospiraceae were more enriched in cecum. The proportions of Deltaproteobacteria were increased in cecal microbiota of 2-year-old rats compared to 74-week-old rats.

Major regional distinctions of microbiota between ileum and cecum of old rats appear consistent with those of young rats. Age-related alterations of gut microbiota in old rats seem to occur in minor compositions.

• Aging
• Cecum
• Gastrointestinal microbiome
• Ileum
• Rats

Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment.

Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact.

The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects.

AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.

• CKD
• Microbiota
• Tight junction
• Toll-like receptor
• Uremic toxin

• Trp metabolism
• aryl hydrocarbon receptor
• gut microbiota
• intestinal immunity
• intestinal inflammation

• Animals
• Bacteria/metabolism
• Bacterial Physiological Phenomena
• Disease Susceptibility
• Energy Metabolism
• Gastrointestinal Microbiome
• Homeostasis
• Host-Pathogen Interactions/immunology
• Humans
• Immunity, Mucosal
• Intestines/microbiology
• Intestines/physiology
• Microbiota
• Tryptophan/metabolism

The intestine is the shared site of nutrient digestion, microbiota colonization and immune cell location and this geographic proximity contributes to a large extent to their interaction. The onset and development of a great many diseases, such as inflammatory bowel disease and metabolic syndrome, will be caused due to the imbalance of body immune. As competent assistants, the intestinal bacteria are also critical in disease prevention and control. Moreover, the gut commensal bacteria are essential for development and normal operation of immune system and the pathogens are also closely bound up with physiological disorders and diseases mediated by immune imbalance. Understanding how our diet and nutrient affect bacterial composition and dynamic function, and the innate and adaptive status of our immune system, represents not only a research need but also an opportunity or challenge to improve health. Herein, this review focuses on the recent discoveries about intestinal bacteria–immune crosstalk and nutritional regulation on their interplay, with an aim to provide novel insights that can aid in understanding their interactions.

• bacteria
• crosstalk
• intestine
• mucosal immunity
• nutrients

The gastrointestinal (GI) tract provides a compartmentalized interface with an enormous repertoire of immune and metabolic activities, where the multicellular structure of the mucosa has acquired mechanisms to sense luminal factors, such as nutrients, microbes, and a variety of host-derived and microbial metabolites. The GI tract is colonized by a complex ecosystem of microorganisms, which have developed a highly coevolved relationship with the host’s cellular and immune system. Intestinal epithelial pattern recognition receptors (PRRs) substantially contribute to tissue homeostasis and immune surveillance. The role of bacteria-derived signals in intestinal epithelial homeostasis and repair has been addressed in mouse models deficient in PRRs and signaling adaptors. While critical for host physiology and the fortification of barrier function, the intestinal microbiota poses a considerable health challenge. Accumulating evidence indicates that dysbiosis is associated with the pathogenesis of numerous GI tract diseases, including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Aberrant signal integration at the epithelial cell level contributes to such diseases. An increased understanding of bacterial-specific structure recognition and signaling mechanisms at the intestinal epithelial interface is of great importance in the translation to future treatment strategies. In this review, we summarize the growing understanding of the regulation and function of the intestinal epithelial barrier, and discuss microbial signaling in the dynamic host–microbe mutualism in both health and disease.

• bacterial signaling
• colorectal cancer
• inflammation
• intestinal epithelium
• intestinal microbiota

• C3
• Chronic colitis
• Inflammatory bowel disease
• Intestinal bacteria
• Intestinal epithelial cells
• LPS
• Toll-like receptors

• Interleukin-10
• Toll-like receptors
• cytokine
• enterocyte
• epithelium
• gut

• Colon cancer
• treatment response
• tumor microenvironment

• mucin-type o-glycans
• mucus layer
• colitis
• microbiota