MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis

Yao, Dianbo; Dai, Weijie; Dong, Ming; Dai, Chaoliu; Wu, Shuodong

doi:10.1016/j.ebiom.2021.103751

Cited by 109 publications

(71 citation statements)

References 93 publications

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“…Occludin is one of the major intestinal tight junction proteins involved in maintaining the structural integrity of the colon ( 29 , 30 ), and is observed to be downregulated during colitis ( 31 ). In addition, deficiency in Muc2 expression leads to spontaneous development of colitis in mice, and diminished mucus production has been observed in IBD patients ( 32 , 33 ). Furthermore, mucin expression has been shown to be inversely correlated with IBD severity and inflammation levels in the gut ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα

et al. 2022

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Inflammatory bowel disease (IBD) is a chronic progressive intestinal inflammatory disease, characterized by an altered gut microbiota composition and accompanying alterations in circulatory bile acids. Increasing evidence supports the beneficial effect of probiotics intake on health. Introduction of probiotics to the intestines can modulate gut microbiota composition and in turn regulate the host immune system and modify the inflammatory response. Probiotics can also improve intestinal barrier function and exhibit a positive impact on host physiological and pathological conditions via gut microbiota-derived metabolites. Previous studies have demonstrated that Lactobacillus casei strain Shirota (LcS) treatment could inhibit clinical manifestation of colitis in dextran sulfate sodium (DSS)-induced mice, however, the underlying mechanisms remain unknown. In this study, we employed the DSS-induced acute colitis mouse model to investigate the anti-inflammatory effects of LcS and related mechanisms. Administration of LcS ameliorated the severity of DSS-induced colitis and enhanced intestinal integrity via induction of mucin-2 and occludin expression in colons. Fecal microbiota analysis showed that LcS increased the relative abundance of beneficial bacterial species in colitic mice, whereas the relative abundance of pathobionts was reduced. Additionally, LcS treatment modulated circulating bile acid profiles in colitic mice. In mice treated with LcS, we identified increased levels of primary taurine-conjugated bile acids, including taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). LcS treatment also increased the levels of secondary taurine-conjugated bile acids, including taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). Moreover, LcS treatment exhibited a suppressive effect on the hydroxylated primary bile acids α-muricholic acid (α-MCA) and β-muricholic acid (β-MCA). We further demonstrated that LcS treatment suppressed the expression of pro-inflammatory mediators interferon-gamma (IFN-γ) and nitric oxide (NO), and increased the expression of the anti-inflammatory mediator interleukin-10 (IL-10) in colon tissues, potentially as a result of altered bile acid profiles. Mechanistically, we showed that LcS treatment suppressed the activation of nuclear factor-kappa B (NF-κB) signaling via stabilization of inhibitor of NF-κB alpha (IκBα). Altogether, we have demonstrated the therapeutic effects of LcS in DSS-induced colitis, providing new insights into its effect on bile acid metabolism and the related anti-inflammatory mechanisms. Our findings provide support for the application of LcS in the treatment of IBD.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα

et al. 2022

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“…Studies have shown that intestinal epithelial barrier dysfunction and impaired tight junction function play a crucial role in pathogenesis of IBD (Sanchez de Medina et al, 2014;Mehandru and Colombel, 2021). Cell proliferation and the expression of tight junction-associated and peripheral membrane proteins (KI67, Occluding, Claudin-1, ZO-1, and MUC2) have been analyzed to determine intestinal barrier function (Tan and Zheng, 2018;Graefe et al, 2019;Yao et al, 2021). The slgA is the intestinal mucosal immune barrier's front line against external pathogens (Kumar et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Early life administration of Bifidobacterium bifidum BD-1 alleviates long-term colitis by remodeling the gut microbiota and promoting intestinal barrier development

Peng

Miao

et al. 2022

Front. Microbiol.

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Inflammatory bowel disease (IBD) is a chronic intestinal disease characterized by microbiota disturbance and intestinal mucosal damage. The current study aimed to investigate the preventive effects of Bifidobacterium bifidum BD-1 (BD-1) against long-term IBD and possible mechanism by which it alters the gut microbiota, immune response, and mucosal barrier. Our study found that early treatment of BD-1 + Ceftri (ceftriaxone followed by BD-1) and BD-1 confers a certain protective effect against the occurrence of long-term Dextran sulfate sodium-induced colitis, which manifests as a decrease in inflammation scores and MPO activity levels, as well as a relatively intact intestinal epithelial structure. Moreover, compared to BD-1, Ceftri, and NS, early treatment with BD-1 + Ceftri promoted greater expression levels of mucosal barrier-related proteins [KI67, MUC2, ZO-1, secretory immunoglobulin A (slgA), Clauding-1, and Occludin], better local immune responses activation, and moderately better modulation of systemic immune responses during long-term colitis. This may be due to the fact that BD-1 + Ceftri can deliberately prolong the colonization time of some beneficial microbiota (e.g., Bifidobacterium) and reduce the relative abundance of inflammation-related microbiota (e.g., Escherichia/Shigella and Ruminococcus). Interestingly, we found that the changes in the gut barrier and immunity were already present immediately after early intervention with BD-1 + Ceftri, implying that early effects can persist with appropriate intervention. Furthermore, intervention with BD-1 alone in early life confers an anti-inflammatory effect to a certain degree in the long-term, which may be due to the interaction between BD-1 and the host’s native gut microbiota affecting intestinal metabolites. In conclusion, BD-1 was not as effective as BD-1 + Ceftri in early life, perhaps due to its failure to fully play the role of the strain itself under the influence of the host’s complex microbiota. Therefore, further research is needed to explore specific mechanisms for single strain and native microbiota or the combination between probiotics and antibiotics.

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“…The mucus layer is formed by mucins combined with water, inorganic salts, and antimicrobial peptides, which could protect the gastrointestinal tract from invading pathogens and promote the development of the intestine ( 33 ). MUC2 is the main protein component of the intestinal mucus and can provide a physical barrier between the epithelium and the luminal content ( 34 ). The results of this study showed that the number of goblet cells in the intestine of the PNZ- and ZO-supplemented groups was increased.…”

Section: Discussionmentioning

confidence: 99%

Dietary Palygorskite Clay-Adsorbed Nano-ZnO Supplementation Improves the Intestinal Barrier Function of Weanling Pigs

Mao

et al. 2022

Front. Nutr.

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This study aimed to investigate the effects of PNZ on intestinal mucosal barrier function in weaning piglets. A total of 210, 21-day-old piglets with similar body weights (6.30 ± 0.51 kg) were randomly allocated into seven groups: control group (CON), antibiotic group (ANT), ZnO group (ZO), nano-ZnO group (NZO) and low, middle, and high PNZ groups (LPNZ, MPNZ, and HPNZ). The seven groups were, respectively, fed control diets or control diets supplemented with antibiotics; 3,000 mg/kg ZnO; 800 mg/kg nano-ZnO; 700, 1,000, or 1,300 mg/kg PNZ. More integrated intestinal villi were observed in the LPNZ group. In the jejunum of LPNZ group, the crypt depth significantly decreased (P < 0.05), and the ratio of villus height to crypt depth (V/C) significantly increased (P < 0.05). In addition, the villus width and surface area of the ileum were significantly increased in the LPNZ group (P < 0.05). Dietary supplementation with PNZ can significantly increase the number of goblet cells in the mucosa of the jejunum and ileum (P < 0.05), decrease the contents of TNF-α and IL-1β (P < 0.05), and increase the contents of sIgA and IL-4 in the jejunal and ileal mucosa (P < 0.05). Meanwhile, the mRNA expression of MCU2 and ZO1 in PNZ group were significantly increased (P < 0.05), the mRNA expression of TLR4 and MyD88 was downregulated (P < 0.05). With increasing levels of PNZ, decreased proinflammatory cytokines and increased intestinal mucosal barrier function in weaned pigs was observed. In conclusion, supplementation with PNZ could effectively improve the intestinal barrier function of weanling piglets and potentially could replace the use of high doses of ZnO and antibiotics. The appropriate dose of PNZ for supplementation was 700 mg/kg.

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MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis

Cited by 109 publications

References 93 publications

Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα

Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα

Early life administration of Bifidobacterium bifidum BD-1 alleviates long-term colitis by remodeling the gut microbiota and promoting intestinal barrier development

Dietary Palygorskite Clay-Adsorbed Nano-ZnO Supplementation Improves the Intestinal Barrier Function of Weanling Pigs

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