Sodium Butyrate Alleviates Mouse Colitis by Regulating Gut Microbiota Dysbiosis

Inflammatory bowel disease (IBD) develops as a result of complicated interactions between genetic susceptibility, excessive innate immunity, and environmental factors, which are mainly related to the gut microbiota. The present study aimed to elucidate the protective effects and underlying mechanisms of a short-chain fatty acid salt, sodium butyrate, on colonic inflammation induced by dextran sulfate sodium (DSS) in mice. Pretreatment with sodium butyrate attenuated colitis, as demonstrated by the decreased disease activity index (DAI), colon length shortening, spleen tumidness, and histopathology scores, while maintaining intestinal barrier integrity, as observed by H&E staining and electron microscopy. 16S rRNA sequence analysis revealed that sodium butyrate caused a remarkable alteration of the gut microbiota. Bacteroides, Lachnospiraceae, the Lachnospiraceae NK4A136 group, and Ruminiclostridium 6 presented dramatic differences after sodium butyrate supplementation. This work verifies that sodium butyrate can improve mouse colitis via microbe–host interactions by regulating the microbial community. Taken together, the findings demonstrate that sodium butyrate shows great potential as a probiotic agent for ameliorating colitis.

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Bacillus licheniformis Zhengchangsheng® attenuates DSS-induced colitis and modulates the gut microbiota in mice

Beneficial Microbes ◽

10.3920/bm2018.0122 ◽

2019 ◽

Vol 10 (5) ◽

pp. 543-553 ◽

Cited By ~ 3

Author(s):

Y. Li ◽

M. Liu ◽

J. Zhou ◽

B. Hou ◽

X. Su ◽

...

Keyword(s):

Gut Microbiota ◽

Bacillus Licheniformis ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Experimental Colitis ◽

Valuable Insight ◽

Microbial Composition ◽

Gastrointestinal Health ◽

Human Inflammatory Bowel Disease

Human inflammatory bowel disease (IBD) and experimental colitis models in mice are associated with shifts in gut microbiota composition, and several probiotics are widely used to improve gastrointestinal health. Here, we investigated whether the probiotic Bacillus licheniformis Zhengchangsheng® (BL) ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota. Experimental colitis was induced in BALB/C mice by dissolving 3% DSS in their drinking water for 7 days, which were gavaged with 0.2 ml phosphate-buffered saline or BL (3×107 cfu/ml) once a day. Administration of BL attenuated several effects of DSS-induced colitis, including weight loss, increased disease activity index, and disrupted intestinal barrier integrity. In addition, BL mitigated the reduction in faecal microbiota richness in DSS treated mice. Interestingly, BL was found to reduce the elevated circulating endotoxin level in mice with colitis by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Bacteroidetes. Our results demonstrate that BL can attenuate DSS-induced colitis and provide valuable insight into microbiota interactions during IBD.

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Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Mediators of Inflammation ◽

10.1155/2020/7605160 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jingxuan Sun ◽

Boyu Yuan ◽

Yancheng Wu ◽

Yuhong Gong ◽

Wenjin Guo ◽

...

Keyword(s):

Sodium Butyrate ◽

Cell Injury ◽

Cell Damage ◽

Protective Effects ◽

Neuroprotective Effects ◽

Fatty Acid Salt ◽

Cognitive Improvement ◽

N2a Cells ◽

Underlying Mechanisms

Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

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Dietary Bioactive Peptide Alanyl-Glutamine Attenuates Dextran Sodium Sulfate-Induced Colitis by Modulating Gut Microbiota

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5543003 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Qingbiao Xu ◽

Mingyang Hu ◽

Min Li ◽

Jinxiu Hou ◽

Xianghua Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Activity Index ◽

Intestinal Barrier ◽

Body Weight Loss ◽

Community Diversity ◽

Peptide Transporter ◽

Protective Effects ◽

Gut Health ◽

Beneficial Effects ◽

Rdna Sequencing

Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di-peptide alanyl-glutamine (Ala-Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala-Gln and glutamine (Gln) on dextran sulfate sodium- (DSS-) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala-Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin- (IL-) 1β, IL-6, tumor necrosis factor-α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala-Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala-Gln or Gln. Interestingly, Ala-Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS-induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala-Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala-Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala-Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.

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Anti-Inflammatory Effects of Heritiera littoralis Fruits on Dextran Sulfate Sodium- (DSS-) Induced Ulcerative Colitis in Mice by Regulating Gut Microbiota and Suppressing NF-κB Pathway

BioMed Research International ◽

10.1155/2020/8893621 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20

Author(s):

Guosheng Lin ◽

Minyao Li ◽

Nan Xu ◽

Xiaoli Wu ◽

Jingjing Liu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Disease Activity Index ◽

Rrna Gene ◽

Chemical Compositions ◽

Protective Effects ◽

Esi Ms

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway.

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New pathway ameliorating ulcerative colitis: focus on Roseburia intestinalis and the gut–brain axis

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211004469 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110044

Author(s):

Fenghua Xu ◽

Yi Cheng ◽

Guangcong Ruan ◽

Liqin Fan ◽

Yuting Tian ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Rrna Sequencing ◽

Key Factor ◽

Behavioral Assays ◽

Immunohistochemical Analyses

Background: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut–brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. Methods: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut–brain axis. Results: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. Conclusions: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut–brain axis.

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Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Nutrients ◽

10.3390/nu13030773 ◽

2021 ◽

Vol 13 (3) ◽

pp. 773

Author(s):

Jacob P. Veenstra ◽

Bhaskar Vemu ◽

Restituto Tocmo ◽

Mirielle C. Nauman ◽

Jeremy J. Johnson

Keyword(s):

Disease Activity ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Carnosic Acid ◽

Rosemary Extract ◽

Oral Gavage ◽

Barrier Integrity ◽

Dietary Phytochemicals ◽

Intestinal Barrier Integrity

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.

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Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

BioMed Research International ◽

10.1155/2021/5561221 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xinghan Zheng ◽

Liting Mai ◽

Tongtong Wang ◽

Ying Xu ◽

Zireng Su ◽

...

Keyword(s):

Signaling Pathways ◽

Activity Index ◽

Disease Activity Index ◽

Protective Effects ◽

Intestinal Epithelial ◽

Colon Tissue ◽

Epithelial Barrier Function ◽

Brucea Javanica ◽

Tnf Α ◽

Brucea Javanica Oil

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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The Adipokine Metrnl Ameliorates Chronic Colitis in Il-10–/– Mice by Attenuating Mesenteric Adipose Tissue Lesions During Spontaneous Colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz001 ◽

2019 ◽

Vol 13 (7) ◽

pp. 931-941 ◽

Cited By ~ 4

Author(s):

Lugen Zuo ◽

Sitang Ge ◽

Yuanyuan Ge ◽

Jingjing Li ◽

Bing Zhu ◽

...

Keyword(s):

Adipose Tissue ◽

Activity Index ◽

Disease Activity Index ◽

Experimental Colitis ◽

Protective Effects ◽

Systemic Delivery ◽

Chronic Colitis ◽

Mesenteric Adipose Tissue ◽

Proinflammatory Mediators ◽

Ppar Γ

Abstract Background Crosstalk between mesenteric adipose tissue [MAT] and the intestines affects the progression of Crohn’s disease [CD]. The adipokine metrnl regulates adipocyte function and has anti-inflammatory activity. We aimed to explore metrnl expression in CD MAT, investigate the influence of metrnl on the experimental colitis disease course and determine the mechanism underlying this effect. Methods Metrnl expression in MAT specimens obtained from patients with and without CD was tested by immunohistochemistry. Male Il-10–/– mice with spontaneous enteritis were divided into positive control and metrnl-treated [Metrnl-Fc, 10 mg/kg/d, intraperitoneally, 8 weeks] groups. Age-matched male wild-type [WT] mice were used as negative controls. The effects of metrnl on enteritis and mesenteric lesions and the potential controlling mechanisms were evaluated. Results Metrnl expression was higher in human CD MAT than in control MAT. Systemic delivery of metrnl significantly ameliorated chronic colitis in Il-10–/– mice, as demonstrated by decreases in the disease activity index, inflammatory score and proinflammatory mediators. The protective effects of metrnl on MAT included reduced mesenteric hypertrophy, increased adipocyte size, improved adipocyte intrinsic function and ameliorated inflammation. Metrnl treatment activated STAT5/PPAR-γ signaling and promoted adipocyte differentiation in the MAT. Conclusions Metrnl expression was increased in the MAT of CD patients. Metrnl administration attenuated mesenteric lesions by promoting adipocyte function and differentiation partly through STAT5/PPAR-γ signaling pathway activation, thereby ameliorating CD-like colitis in mice.

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