Initial gut microbiota structure affects sensitivity to DSS-induced colitis in a mouse model

The dextran sulfate sodium (DSS)-induced colitis model is a widely applied mouse model, but controversial results have been obtained from experiments using the same mouse strain under the same conditions. Because the gut microbiota play an important role in DSS-induced colitis, it is essential to evaluate the influence of the initial gut microbiota in this model. Here, we identified significant variations in the initial gut microbiota of different batches of mice and found that the initial intestinal microbiota had a profound influence on DSS-induced colitis. We performed three independent trials using the same C57BL/6J mouse model with DSS treatment and used high-throughput 16S rRNA gene sequencing to analyze the gut microbiota. We found that the structure and composition of the gut microbiota in mice with severe colitis, as compared with mice with milder colon damage, had unique features, such as an increase in Akkermansia bacteria and a decrease in Barnesiella spp. Moreover, these varied gut bacteria in the different trials also showed different responses to DSS treatment. Our work suggests that, in studies using mouse models, the gut microbiota must be considered when examining mechanisms of diseases, to ensure that comparable results are obtained.     

Bioactive constituents of Mosla chinensis-cv. Jiangxiangru ameliorate inflammation through MAPK signaling pathways and modify intestinal microbiota in DSS-induced colitis mice

BackgroundMosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency.PurposeThis study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms.MethodsThe bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E₂ (PGE₂)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored.ResultsTotally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE₂) and cytokines (TNF-α, IL-6, IL-1β). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model.ConclusionsThis study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.     

L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis

Background

Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is characterized by a deregulation of the mucosal immune system and resistance of activated T cells to apoptosis. Current therapeutics show limited efficacy and potential toxicity; therefore there is a need for novel approaches for the treatment of IBD. L-cysteine was examined for its ability to reduce colitis symptoms and modulate local gene expression in a DSS-induced porcine model of colitis.

Methods

Colitis was induced via intra-gastric infusion of dextran sodium sulfate (DSS), followed by the administration of L-cysteine or saline. Clinical signs, morphological measurements, histology and gut permeability were assessed for the prognosis of colitis. Local tissue production of cytokines and gene expression in the colon were analyzed by ELISA and real-time RT-PCR.

Results

L-cysteine supplementation attenuated DSS-induced weight loss and intestinal permeability, reduced local chemokine expression and neutrophil influx, and markedly improved colon histology. Furthermore, cysteine significantly reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-6, IL-12p40, IL-1β, and resulted in increased expression of the apoptosis initiator caspase-8 and decreased expression of the pro-survival genes cFLIP and Bcl-xL.

Conclusions and general significance

These results suggest that L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restoring susceptibility of activated immune cells to apoptosis, and that cysteine supplementation may be a novel therapeutic strategy for the treatment of IBD.     

Berberine ameliorates DSS-induced intestinal mucosal barrier dysfunction through microbiota-dependence and Wnt/β-catenin pathway

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/β-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/β-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.     

Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris

Background: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive.Purpose: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms.Methods: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis.Results: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/β-catenin signaling via alleviating the overexpression of β-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis.Conclusion: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.     

嗜粘蛋白阿克曼菌在糖尿病和肥胖中的作用

肠道微生物在平衡健康与疾病的过程中起着重要作用。嗜粘蛋白阿克曼菌(Akkermansia muciniphila)是肠道微生物中的一种,其在降解肠道粘蛋白方面的特性使其成为肠腔与宿主细胞黏膜界面的关键生物。嗜粘蛋白阿克曼菌与肥胖、糖尿病、心血管代谢疾病和低度炎症呈负相关。口服嗜粘蛋白阿克曼菌可改善小鼠代谢疾病的相关症状,嗜粘蛋白阿克曼菌有望成为治疗2型糖尿病和肥胖的候选药物。本综述通过总结现有关于嗜粘蛋白阿克曼菌在糖尿病和肥胖症中发挥作用的研究,指出嗜粘蛋白阿克曼菌调节宿主和肠道微生物群之间相互作用可能存在的机制,为嗜粘蛋白阿克曼菌的进一步研究和糖尿病的新药研发提供思路。     

Lentinula edodes-Derived Polysaccharide Alters the Spatial Structure of Gut Microbiota in Mice

Lentinula edodes-derived polysaccharides possess many therapeutic characteristics, including anti-tumor and immuno-modulation. The gut microbes play a critical role in modulation of immune function. However, the impact of Lentinula edodes-derived polysaccharides on the gut microbes have not yet been explored. In this study, high-throughput pyrosequencing technique was employed to investigate the effects of a new heteropolysaccharide L2 from Lentinula edodes on microbiota diversity and composition of small intestine, cecum, colon and distal end of colon (feces) in mice. The results demonstrated that along mouse intestine the microbiota exhibit distinctly different space distribution. L2 treatment reduced the diversity and evenness of gut microbiota along the intestine, especially in the cecum and colon. In the fecal microbial communities, the decrease of Bacteroidetes by significantly increasing Proteobacteria were observed, which were characterized by the increased Helicobacteraceae and reduced S24-7 at family level. Some OTUs, corresponding to Bacteroides acidifaciens, Alistipes and Helicobacter suncus, were found to be significantly increased in L2 treated-mice. In particular, 4 phyla Chloroflexi, Gemmatimonadetes, Nitrospirae and Planctomycetes are exclusively present in L2-treated mice. This is helpful for further demonstrating healthy action mechanism of Lentinula edodes-derived polysaccharide L2.     

Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice,which is further aggravated by supplementation of heme

The Western diet, rich in fat and red meat, predisposes for inflammatory bowel disease (IBD); however, little is known about mechanisms involved. Red meat contains high levels of heme, a well-known inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1). Pharmacological induction of HO-1 ameliorates experimental colitis. We analyzed the effect of a westernized high-fat (HF) diet supplemented with heme on intestinal HO-1 expression and dextran sulfate sodium (DSS)-induced colitis.Mice were fed chow or HF diets for 2 weeks. In the second week, the HF diet was supplemented with or without 0.5 μmol/g heme. Subsequently, the 3 diet groups were given drinking water with or without 4% DSS to induce colitis.Significant body weight reduction was first observed after 4 days in the chow/DSS mice (?5±3%), whereas this was evident already after 2 days (?6±2%) in HF/DSS mice, showing increased weight loss compared to chow/DSS mice in the following days. Heme supplementation further aggravated DSS-induced weight loss in HF mice (?18±4% vs. ?7±5% for HF+heme/DSS vs. HF/DSS, P<.01). Heme increased HO-1 expression in the colon epithelium but decreased villin messenger RNA levels, indicating epithelial damage. In contrast, heme did not affect DSS-induced colon shortening and histological scores of epithelial damage and inflammation.A westernized diet accelerates DSS-induced weight loss in mice, which is further aggravated by heme, despite the induction of HO-1 in the colon epithelium. Our data warrant a detailed analysis of the association of (red) meat-containing diets and the development of IBD.     

Microbial fingerprinting detects unique bacterial communities in the faecal microbiota of rats with experimentally-induced colitis

An abnormal composition of the gut microbiota is believed to be associated with the pathogenesis of inflammatory bowel disease (IBD). We utilized terminal restriction fragment length polymorphism (T-RFLP) analysis to quantify faecal bacterial communities from rats with experimental colitis. Male Sprague Dawley rats (n=10/group) ingested 2% dextran sulfate sodium (DSS) or water for up to 7 days. Rats were killed and colonic tissues collected for histological analysis. Damage severity score in the distal colon was significantly greater (P<0.001) following DSS consumption compared to controls. T-RFLP faecal bacterial profiles generated with either MspI or CfoI revealed a significant difference (P<0.001) in community composition between healthy and colitic rats, with bacterial composition in healthy rats more variable than in rats with colitis. Operational taxonomic units (OTU: taxonomically related groups of bacteria) associated with either the healthy or colitic state were identified. OTU (116, 226, 360, and 948; CfoI) and (118 and 188; MspI) were strongly associated with untreated healthy rats, while OTU (94, 98, 174, and 384; CfoI) and (94 and 914; MspI) were predominantly associated with DSS-treated colitic rats. Phylogenetic OTU assignment suggested that Bacteroidales and Lactobacillus sp. were predominantly associated with the colitic and healthy rats, respectively. These results show that faecal bacterial profiling is a rapid, sensitive and non-invasive tool for detecting and identifying changes in gut microbiota associated with colitis. Restoring microbial homeostasis by targeting colitis-associated OTU through specific microbiological interventions could form the basis of novel therapeutic strategies for IBD.     

Treatment with Extracellular Vesicles from Giardia lamblia Alleviates Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.     

Soy protein concentrate mitigates markers of colonic inflammation and loss of gut barrier function in vitro and in vivo

Whereas a number of studies have examined the effects of soy isoflavones and tocopherols on colonic inflammation, few have examined soy protein. We determined the radical scavenging and cytoprotective effects of soy protein concentrate (SPC) in vitro and its anti-inflammatory effects in dextran sulfate sodium (DSS)-treated mice. Cotreatment with SPC protected Caco-2 human colon cells from H₂O₂-induced cell death and mitigated intracellular oxidative stress. Treatment of differentiated Caco-2 cells with SPC blunted DSS-induced increases in monolayer permeability. Pepsin/pancreatin-digested SPC had reduced radical scavenging activity, but retained the monolayer protective effects of SPC. In vivo, 1.5% DSS caused body weight loss, colon shortening, and splenomegaly in CF-1 mice. Co-treatment with 12% SPC mitigated DSS-induced body weight loss and splenomegaly. DSS increased colonic interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 expression. The levels of these markers were significantly lower in mice co-treated with SPC. SPC prevented DSS-mediated reductions in colonic glucagon-like peptide 2 levels, suggesting that SPC can prevent loss of gut barrier function, but no significant effect on claudin 1 and occludin mRNA levels of was observed. SPC-treated mice had lower colonic mRNA expression of toll-like receptor 4 and nucleotide-binding oligomerization domain-containing protein-like receptor family, pyrin domain containing protein 3 (NLRP3), and lower caspase-1 enzyme activity than DSS-treated mice. In summary, SPC exerted antioxidant and cytoprotective effects in vitro and moderated the severity of DSS-induced inflammation and loss of gut barrier function in vivo. These effects appear to be mediated in part through reduced NLRP3 expression and caspase 1 activity.     

Anthocyanin-containing purple potatoes ameliorate DSS-induced colitis in mice

Ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD), is on the rise worldwide. Approximately three million people suffer from IBD in the United States alone, but the current therapeutic options (e.g., corticosteroids) come with adverse side effects including reduced ability to fight infections. Thus, there is a critical need for developing effective, safe and evidence-based food products with anti-inflammatory activity. This study evaluated the antiinflammatory potential of purple-fleshed potato using a dextran sodium sulfate (DSS) murine model of colitis. Mice were randomly assigned to control (AIN-93G diet), P15 (15% purple-fleshed potato diet) and P25 (25% purple-fleshed potato diet) groups. Colitis was induced by 2% DSS administration in drinking water for six days. The results indicated that purple-fleshed potato supplementation suppressed the DSS-induced reduction in body weight and colon length as well as the increase in spleen and liver weights. P15 and P25 diets suppressed the elevation in the intestinal permeability, colonic MPO activity, mRNA expression and protein levels of pro-inflammatory interleukins IL-6 and IL-17, the relative abundance of specific pathogenic bacteria such as Enterobacteriaceae, Escherichia coli (E. coli) and pks⁺ E. coli, and the increased flagellin levels induced by DSS treatment. P25 alone suppressed the elevated systemic MPO levels in DSS-exposed mice, and elevated the relative abundance of Akkermansia muciniphila (A. muciniphila) as well as attenuated colonic mRNA expression level of IL-17 and the protein levels of IL-6 and IL-1β. Therefore, the purple-fleshed potato has the potential to aid in the amelioration of UC symptoms.     

Effect of Metformin on Metabolic Improvement and Gut Microbiota

Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44% ± 5.26%) and Clostridium cocleatum (0.10% ± 0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.     

Intestinal anti-inflammatory effect of the probiotic Saccharomyces boulardii in DSS-induced colitis in mice: Impact on microRNAs expression and gut microbiota composition

The beneficial effects exerted by probiotics in inflammatory bowel disease (IBD) are well known, although their exact mechanisms have not been fully elucidated, and only few studies have focused on their impact on selected miRNAs and the gut microbiota composition. Therefore, our aim was to correlate the intestinal anti-inflammatory activity of the probiotic Saccharomyces boulardii in the dextran sodium sulphate (DSS) model of mouse colitis and the changes induced in miRNA expression and gut microbiota populations. Probiotic was given orally (5×10⁹ CFU) to C57BL/6 mice for 26 days. After 2 weeks, the colitis was induced adding DSS to the drinking water. Mice were scored daily using a Disease Activity Index (DAI). After sacrifice, the colonic specimens were evaluated by determining the expression of inflammatory markers and micro-RNAs by qRT-PCR. Moreover, changes in microbiota populations were evaluated by pyrosequencing. Probiotic ameliorated the colonic damage induced by DSS, as evidenced by lower DAI values and colonic weight/length compared with untreated mice. The treatment modified the colonic expression of different inflammatory markers and the epithelial integrity proteins, and induced changes in micro-RNAs expression. Moreover, microbiota characterization showed that probiotic treatment increased bacterial diversity, thus ameliorating the dysbiosis produced by DSS-colitis. Saccharomyces boulardii exerted intestinal anti-inflammatory effects in DSS-mouse colitis, through the modulation in the immune response, involving modification of altered miRNA expression, being associated to the improvement of the inflammation-associated dysbiosis in the intestinal lumen, which could be of great interest to control the complex pathogenesis of IBD.     

Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-alpha), exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis

The role of TLRs and MyD88 in the maintenance of gut integrity in response to dextran sodium sulfate (DSS)-induced colitis was demonstrated recently and led to the conclusion that the innate immune response to luminal commensal flora provides necessary signals that facilitate epithelial repair and permits a return to homeostasis after colonic injury. In this report, we demonstrate that a deficit in a single neutrophil chemokine, CXCL1/KC, also results in a greatly exaggerated response to DSS. Mice with a targeted mutation in the gene that encodes this chemokine responded to 2.5% DSS in their drinking water with significant weight loss, bloody stools, and a complete loss of gut integrity in the proximal and distal colon, accompanied by a predominantly mononuclear infiltrate, with few detectable neutrophils. In contrast, CXCL1/KC(- /-) and wild-type C57BL/6J mice provided water showed no signs of inflammation and, at this concentration of DSS, wild-type mice showed only minimal histopathology, but significantly more infiltrating neutrophils. This finding implies that neutrophil infiltration induced by CXCL1/KC is an essential component of the intestinal response to inflammatory stimuli as well as the ability of the intestine to restore mucosal barrier integrity.     

Vitamin E delta-tocotrienol and metabolite 13’-carboxychromanol inhibit colitis-associated colon tumorigenesis and modulate gut microbiota in mice

The gut microbiota play important roles in colon cancer. Vitamin E δ-tocotrienol (δTE) and its metabolite δTE-13′-carboxychromanol (δTE-13′) are known to have cancer-preventive effects, but their impact on gut flora during tumorigenesis and the role of the metabolite in δTE's beneficial effects remain to be determined. In the murine colitis-associated colon cancer (CAC) induced by azoxymethane (AOM) and dextran sulfate sodium (DSS), we show that δTE and δTE-13′ inhibited the multiplicity of large adenomas (>2 mm²) by 34% (P<.05) and 55% (P<.01), respectively, compared to the control diet. δTE-13’ diminished AOM/DSS-increased GM-CSF and MCP-1, and δTE decreased IL-1β. Using 16S rRNA gene sequencing of fecal DNAs, we observe that δTE and δTE-13′ modulated the composition but not the richness of gut microbes compared to the control. Both δTE and δTE-13′ enhanced potentially beneficial Lactococcus and Bacteroides. The elevation of Lactococcus positively correlated with fecal concentrations of δTE-13′ and its hydrogenated metabolite, suggesting that the metabolite may contribute to δTE's modulation of gut microbes. Furthermore, δTE-13’ counteracted AOM/DSS-induced depletion of Roseburia that is known to be decreased in patients with inflammatory bowel diseases. δTE uniquely elevated (Eubacterium) coprostanoloigenes. Our study demonstrates that δTE and δTE-13′ inhibited tumorigenesis, suppressed pro-inflammatory cytokines and modulated gut microbiota in a murine CAC model. These findings uncover new and distinct activities of δTE and δTE-13′ and support the notion that the metabolite may play a role in δTE's anticancer and modulation of gut microbes.     

Altered Mucus Glycosylation in Core 1 O-Glycan-Deficient Mice Affects Microbiota Composition and Intestinal Architecture

A functional mucus layer is a key requirement for gastrointestinal health as it serves as a barrier against bacterial invasion and subsequent inflammation. Recent findings suggest that mucus composition may pose an important selection pressure on the gut microbiota and that altered mucus thickness or properties such as glycosylation lead to intestinal inflammation dependent on bacteria. Here we used TM-IEC C1galt ^-/- mice, which carry an inducible deficiency of core 1-derived O-glycans in intestinal epithelial cells, to investigate the effects of mucus glycosylation on susceptibility to intestinal inflammation, gut microbial ecology and host physiology. We found that TM-IEC C1galt ^-/- mice did not develop spontaneous colitis, but they were more susceptible to dextran sodium sulphate-induced colitis. Furthermore, loss of core 1-derived O-glycans induced inverse shifts in the abundance of the phyla Bacteroidetes and Firmicutes. We also found that mucus glycosylation impacts intestinal architecture as TM-IEC C1galt^-/- mice had an elongated gastrointestinal tract with deeper ileal crypts, a small increase in the number of proliferative epithelial cells and thicker circular muscle layers in both the ileum and colon. Alterations in the length of the gastrointestinal tract were partly dependent on the microbiota. Thus, the mucus layer plays a role in the regulation of gut microbiota composition, balancing intestinal inflammation, and affects gut architecture.