• Ganoderma lucidum
• active ingredients
• gut flora
• medicinal value
• regulation

• non-digestible carbohydrates
• prebiotics
• short-chain fatty acids (SCFA)

• Inflammatory bowel disease
• machine learning
• microbiota
• ulcerative colitis

• dysbacteriosis
• ethnic group
• gut microflora
• microbial diversity
• ulcerative colitis

• Adult
• Bacteria/genetics
• Bacteria/isolation & purification
• China/epidemiology
• Colitis, Ulcerative/ethnology
• Colitis, Ulcerative/microbiology
• Ethnicity
• Female
• Gastrointestinal Microbiome
• Humans
• Incidence
• Male
• Middle Aged
• RNA, Ribosomal, 16S/genetics
• RNA, Ribosomal, 16S/metabolism
• Retrospective Studies
• Young Adult

• 81760101 National Natural Science Foundation of China

Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning.

We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4⁺ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated–NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria.

We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).

• Acute Disease
• Adoptive Transfer
• Animals
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use
• Bacteria/classification
• Bacteria/drug effects
• Bacteria/growth & development
• Blood Cell Count
• Bone Marrow/drug effects
• Bone Marrow/pathology
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/microbiology
• Cytokines/blood
• Disease Progression
• Feces/microbiology
• Graft vs Host Disease/blood
• Graft vs Host Disease/complications
• Graft vs Host Disease/drug therapy
• Graft vs Host Disease/pathology
• Inflammation/blood
• Inflammation/complications
• Inflammation/pathology
• Lymphopenia/blood
• Lymphopenia/complications
• Lymphopenia/drug therapy
• Male
• Mice
• Phylogeny
• Spleen/drug effects
• Spleen/pathology
• Transplantation, Homologous

• F31 AI145077 NIAID NIH HHS
• national institute of allergy and infectious disease (niaid)

Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between the gut microbiota and the host remains poorly understood. Increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease. The intestinal proteolytic balance is the result of an equilibrium between the proteases and their corresponding inhibitors. Interestingly, the serine protease inhibitors (serpins) encoded by the host are well reported; in contrast, those from the gut microbiota remain poorly studied. In this review, we provide a concise analysis of the roles of serine protease in IBD physiopathology and we focus on the serpins from the gut microbiota (gut serpinome) and their relevance as a promising therapeutic approach.

• gut microbiota
• gut serpinome
• holobiont
• inflammatory bowel diseases
• proteases

• Animals
• Gastrointestinal Microbiome
• Humans
• Inflammatory Bowel Diseases/physiopathology
• Serine Proteases/chemistry
• Serpins/metabolism

Lactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS).

16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.

LGG co-association had a negative impact on colonization of P. acnes, and markedly altered the metabolic output and inflammatory response elicited by pathobionts.

The online version contains supplementary material available at 10.1186/s12866-021-02178-2.

• Competitive exclusion
• Fecal metabolites
• Germ-free mice
• Inflammation
• Liquid chromatography, mass spectrometry
• Microbiota
• Propionibacterium acnes

• gut microbiota
• patchouli alcohol
• patchouli essential oil
• pogostone
• β-patchoulene

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.

The gut microbiome is an important regulator of metabolic health. Here the authors show that intestinal bacteria metabolize dietary linoleic acid to 10-hydroxy-cis-12-octadecenoic acid (HYA) which confers host resistance to high fat diet-induced obesity in mice.

• Clostridium difficile infection
• fecal microbiota transplantation
• inflammatory bowel disease

• butyrate
• microbiota
• model culture systems
• probiotics
• ulcerative colitis

Increasing evidence suggests that intestinal microbiota have critical function in the pathogenesis of inflammatory bowel disease. This present study investigated the effects of Escherichia coli (E. coli) in mice with dextran sulfate sodium (DSS)-induced colitis. Furthermore, Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) gene expression was measured by reverse transcription-quantitative polymerase chain reaction. In total, two experiments were performed. In the first experiment, four groups were established in BALB/c mice: i) Group A, control (no treatments); ii) group B, DSS-induced colitis; iii) group C, DSS-induced colitis bacteria depleted (BD) mice; and iv) group D, E. coli-treated DSS-induced colitis BD mice. In the second experiment, there were three groups: i) Group A1, control C57BL/6 mice; ii) group B1, E. coli-treated DSS-induced colitis BD C57BL/6 mice; and iii) E. coli-treated DSS-induced colitis BD TLR4^−/− mice. Clinical outcomes, colon and immune histopathology and tissue myeloperoxidase activity were assessed. Mice with DSS-induced colitis that were treated with E. coli exhibited enhanced recovery, with significantly improved clinical and histological scores compared with the DSS only group. The mRNA expression of TLR4 and NF-κB in the E. coli-treated group was also significantly higher. These effects were abolished in TLR4^−/− mice, suggesting that E. coli may have promoted recovery through the TLR4 pathway. The present study indicated that E. coli promoted recovery from DSS-induced colitis in mice, potentially through activation of the TLR4/NF-κB signaling pathway.

The Twin Simulator of the Human Intestinal Microbial Ecosystem (TWINSHIME^®) was initially developed to study the luminal gut microbiota of the ascending (AC), transverse (TC), and descending (DC) colon regions. Given the unique composition and potential importance of the mucosal microbiota for human health, the TWINSHIME was recently adapted to simulate the mucosal microbiota as well as the luminal community. It has been previously demonstrated that the luminal community in the TWINSHIME reaches a steady state within two weeks post inoculation, and is able to differentiate into region specific communities. However, less is known regarding the mucosal community structure and dynamics. During the current study, the luminal and mucosal communities in each region of the TWINSHIME were evaluated over the course of six weeks. Based on 16S rRNA gene sequencing and short chain fatty acid analysis, it was determined that both the luminal and mucosal communities reached stability 10–20 days after inoculation, and remained stable until the end of the experiment. Bioinformatics analysis revealed the formation of unique community structures between the mucosal and luminal phases in all three colon regions, yet these communities were similar to the inoculum. Specific colonizers of the mucus mainly belonged to the Firmicutes phylum and included Lachnospiraceae (AC/TC/DC), Ruminococcaceae and Eubacteriaceae (AC), Lactobacillaceae (AC/TC), Clostridiaceae and Erysipelotrichaceae (TC/DC). In contrast, Bacteroidaceae were enriched in the gut lumen of all three colon regions. The unique profile of short chain fatty acid (SCFA) production further demonstrated system stability, but also proved to be an area of marked differences between the in vitro system and in vivo reports. Results of this study demonstrate that it is possible to replicate the community structure and composition of the gut microbiota in vitro. Through implementation of this system, the human gut microbiota can be studied in a dynamic and continuous fashion.

• Bacteroidaceae/classification
• Bacteroidaceae/genetics
• Bacteroidaceae/growth & development
• Batch Cell Culture Techniques
• Bioreactors
• Colon/microbiology
• Computational Biology/methods
• Fatty Acids, Volatile/biosynthesis
• Fatty Acids, Volatile/classification
• Feces/microbiology
• Firmicutes/classification
• Firmicutes/genetics
• Firmicutes/growth & development
• Gastrointestinal Microbiome/genetics
• Humans
• Intestinal Mucosa/microbiology
• Microbial Consortia/genetics
• Models, Biological
• RNA, Ribosomal, 16S/genetics
• Sequence Analysis, DNA

• Crohn’s disease
• inflammatory bowel diseases
• microbiota
• mouse models
• ulcerative colitis

• Dysbiosis
• Gut microbiota
• Inflammatory bowel disease
• Pathobiont

Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies.

• Gut microbiota
• IBD
• Mass spectrometry
• Metabolomics
• NMR

• Barrier function
• CD, Crohns disease
• ER stress
• ERAD, ER-associated protein degradation
• EhCP5, Entamoeba histolytica cysteine protease 5
• FAS, fatty acid synthase
• GI, gastrointestinal
• GalNAc, N-Acetylgalactosamine
• Goblet cell
• IBD
• IBD, Inflammatory bowel disease
• Innate defense
• LLO, Listeriolysin O
• LPS, Lipopolysaccharide
• MUC2
• MucBP, Mucin binding proteins
• Mucin
• SCFA, short chain fatty acids
• Secretory response
• UC, Ulcerative colitis
• UPR, unfolded protein response
• Unfolded protein response

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

• Inflammatory bowel disease
• Intestinal microbiota
• Probiotics
• Fecal microbiota transplantation
• Synthetic microbiota transplantation

• Animals
• Biological Therapy/methods
• Feces/microbiology
• Host-Pathogen Interactions
• Humans
• Immunity, Mucosal
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/therapy
• Intestines/immunology
• Intestines/microbiology
• Microbiota
• Probiotics/therapeutic use
• Treatment Outcome

• Akkermasia muciniphila
• Bacteroides sartorii
• Bacteroides thetaiotaomicron
• Clostridium
• Lactobacillus johnsonii
• core 1 O-glycans deficient mice
• dysbiosis
• gut microbiota
• pyrosequencing
• spontaneous colitis

The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists.

• Inflammatory bowel disease
• Mucosal healing
• Deep remission
• Treatment targets
• Clinical activity

• Biomarkers/metabolism
• Decision Support Techniques
• Endoscopy, Gastrointestinal
• Endpoint Determination
• Feces/chemistry
• Humans
• Inflammatory Bowel Diseases/metabolism
• Inflammatory Bowel Diseases/pathology
• Inflammatory Bowel Diseases/therapy
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Predictive Value of Tests
• Remission Induction
• Terminology as Topic
• Treatment Outcome
• Wound Healing

The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.