An orally administered butyrate‐releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium‐induced murine colitis

Simeoli, Raffaele; Raso, Giuseppina Mattace; Pirozzi, Claudio; Lama, Adriano; Santoro, Anna; Russo, Roberto; Montero‐Melendez, Trinidad; Canani, Roberto Berni; Calignano, Antonio; Perretti, Mauro; Meli, Rosaria

doi:10.1111/bph.13637

Cited by 101 publications

(74 citation statements)

References 71 publications

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“…; Simeoli et al . ). Surprisingly, stress induced an increased gene expression of tight junction proteins Cldn1 and Tjp1, even though increased intestinal permeability doesn't necessarily correlate to decreased tight junction gene expression (Golubeva et al .…”

Section: Discussionmentioning

confidence: 97%

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Wouw

Boehme

Lyte

et al. 2018

The Journal of Physiology

543

309

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There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota-derived metabolites play a central role in the communication between microbes and their host, with short-chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.

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Section: Discussionmentioning

confidence: 97%

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Wouw

Boehme

Lyte

et al. 2018

The Journal of Physiology

543

309

View full text Add to dashboard Cite

show abstract

“…There are studies that also show that butyrate plays an important role in regulating the development of colitis, or acting as an agent to mitigate its deleterious effects . For example, oral administration of sodium butyrate into DSS‐induced colitis mice led to reduction of inflammation . Butyrate deficiency was shown to increase susceptibility to the development of colitis .…”

Section: Discussionmentioning

confidence: 99%

Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells

Alrafas

Busbee

Nagarkatti

et al. 2019

Journal of Leukocyte Biology

133

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Inflammatory diseases of the gastrointestinal tract are often associated with microbial dysbiosis. Thus, dietary interactions with intestinal microbiota, to maintain homeostasis, play a crucial role in regulation of clinical disorders such as colitis. In the current study, we investigated if resveratrol, a polyphenol found in a variety of foods and beverages, would reverse microbial dysbiosis induced during colitis. Administration of resveratrol attenuated colonic inflammation and clinical symptoms in the murine model of 2,4,6‐trinitrobenzenesulfonic acid (TNBS)‐induced colitis. Resveratrol treatment in mice with colitis led to an increase in CD4+FOXP3+ and CD4+IL‐10+ T cells, and a decrease in CD4+IFN‐γ+ and CD4+IL‐17+ T cells. 16S rRNA gene sequencing to investigate alterations in the gut microbiota revealed that TNBS caused significant dysbiosis, which was reversed following resveratrol treatment. Analysis of cecal flush revealed that TNBS administration led to an increase in species such as Bacteroides acidifaciens, but decrease in species such as Ruminococcus gnavus and Akkermansia mucinphilia, as well as a decrease in SCFA i‐butyric acid. However, resveratrol treatment restored the gut bacteria back to homeostatic levels, and increased production of i‐butyric acid. Fecal transfer experiments confirmed the protective role of resveratrol‐induced microbiota against colitis inasmuch as such recipient mice were more resistant to TNBS‐colitis and exhibited polarization toward CD4+FOXP3+ T cells and decreases in CD4+IFN‐γ+ and CD4+IL‐17+ T cells. Collectively, these data demonstrate that resveratrol‐mediated attenuation of colitis results from reversal of microbial dysbiosis induced during colitis and such microbiota protect the host from colonic inflammation by inducing Tregs while suppressing inflammatory Th1/Th17 cells.

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“…It has been reported that Glu prevents nonsteroidal anti‐inflammatory drug‐induced enteritis (Amagase et al, ). Moreover, Gln supplementation attenuates experimental colitis due to the inhibition of inflammatory signaling including NF‐κB and STAT, or the inhibition of T‐cell migration (Simeoli et al, ; Steinmann et al, ; Takagi et al, ; Vernia et al, ). In our experiments, both Glu and Gln partially suppressed the A + V‐induced fecal occult bleeding, although the suppression mechanism remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Among the SCFAs, butyric acid is the most important nutrient for the colon epithelium (Kripke, Fox, Berman, Settle, & Rombeau, 1989;Sakata, 1987) and the induction of antimicrobial peptide LL-37 (Canani et al, 2011). Butyric acid has also been reported to improve DSS-induced colitis in mice (Simeoli et al, 2016) and ulcerative colitis (UC) (Canani et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice

et al. 2018

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Antibiotics sometimes exert adverse effects on the pathogenesis of colitis due to the dysbiosis resulting from the disruption of gut homeostasis. However, the precise mechanisms underlying colitogenic effects of antibiotic‐induced colitis are largely unknown. Here, we show a novel murine fecal occult bleeding model induced by the combinatorial treatment of ampicillin and vancomycin, which is accompanied by an enlarged cecum, upregulation of pro‐inflammatory cytokines IL‐6 and IL‐12, a reduction in Ki‐67‐positive epithelial cell number and an increase in the apoptotic cell number in the colon. Moreover, gas chromatography–tandem mass analysis showed that various kinds of metabolites, including glutamic acid and butyric acid, were significantly decreased in the cecal contents. In addition, abundance of butyric acid producer Clostridiales was dramatically reduced in the enlarged cecum. Interestingly, supplementation of monosodium glutamate or its precursor glutamine suppressed colonic IL‐6 and IL‐12, protected from cell apoptosis and prevented fecal occult blood indicating that the reduced level of glutamic acid is a possible mechanism of antibiotic‐induced fecal occult bleeding. Our data showed a novel mechanism of antibiotic‐induced fecal occult bleeding providing a new insight into the clinical application of glutamic acid for the treatment of antibiotic‐induced colitis.

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An orally administered butyrate‐releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium‐induced murine colitis

Abstract: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Cited by 101 publications

References 71 publications

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells

Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice

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