Short-Chain Fatty Acids Activate GPR41 and GPR43 on Intestinal Epithelial Cells to Promote Inflammatory Responses in Mice

Kim, Myung‐Hee Y.; Kang, Seung Goo; Park, Jeong H.; Yanagisawa, Masashi; Kim, Chang H.

doi:10.1053/j.gastro.2013.04.056

Cited by 825 publications

(685 citation statements)

References 29 publications

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“…This activation can provoke an inflammatory and immune response that can be helpful in the setting of an acute infection, but dysregulation can produce an exaggerated response leading to increased gut permeability and increased absorption of neuro-active metabolites. 72,73 SCFAs can also directly activate the sympathetic nervous system through Gpr41 receptors that are found on sympathetic ganglionic neurons. 74 Furthermore, it has been shown that SCFAc can pass through the blood-brain barrier and influence behavior, neural signaling, the production of neurotransmitters and, ultimately, behavior.…”

Section: Effect Of Bacterial Metabolites On the Central Nervous Systemmentioning

confidence: 99%

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Yarandi

Peterson

Treisman

et al. 2016

J Neurogastroenterol Motil

228

134

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Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

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Section: Effect Of Bacterial Metabolites On the Central Nervous Systemmentioning

confidence: 99%

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Yarandi

Peterson

Treisman

et al. 2016

J Neurogastroenterol Motil

228

134

View full text Add to dashboard Cite

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“…In contrast, inhibition of T-cell populations by MSC shIGFBP7 was significantly reduced in CD3 -(59. 49 Figure S1a and Figure 2a,b). To further confirm these results and exclude the possible off-target effects, we used two small interfering RNAs (siRNAs) of different sequences targeting the same transcript of IGFBP7.…”

Section: Mscs Inhibit the Proliferation Of T-cells Through Igfbp7 In mentioning

confidence: 99%

“…Colons were evaluated for macroscopic damage according to the previous report. 7 Stool consistency and rectal bleeding were scored as previously described, 49 with minor modifications: 0 = normal stool; 1 = loose stool; 2 = soft stool; 3 = diarrhoea; and 4 = diarrhoea and anal bleeding. For histopathologic analysis, colon specimens were obtained and stained with H&E. Inflammation was graded as follows: 0 = no sign of inflammation; 1 = low leukocyte infiltration; 2 = moderate leukocyte infiltration; 3 = high leukocyte infiltration, moderate fibrosis, high vascular density, thickening of the colon wall, moderate goblet cell loss, and focal loss of crypts; and 4 = transmural infiltrations, massive loss of goblet cell, extensive fibrosis, and diffuse loss of crypts.…”

Section: Apoptosis Detection Of T-cells and Iecsmentioning

confidence: 99%

Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression

et al. 2016

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Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T-cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor.

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“…Butyrate is responsible for a number of physiologic roles within the gastrointestinal tract, including maintenance of intestinal barrier integrity, regulation of epigenetic gene expression, and mediation of anti-inflammatory responses to oxidative stress [95][96][97]. Alterations of butyrate producing species have been noted in both UC and CD patients with somewhat differing roles.…”

Section: Genetic and Microbial Interactions In Inflammatory Bowel Dismentioning

confidence: 99%

Nature vs. Nurture: The Gut Microbiome and Genetics in the Development of Gastrointestinal Disease

Ec¹,

Da²

2016

J Hepatol Gastroint Dis

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Short-Chain Fatty Acids Activate GPR41 and GPR43 on Intestinal Epithelial Cells to Promote Inflammatory Responses in Mice

Cited by 825 publications

References 29 publications

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression

Nature vs. Nurture: The Gut Microbiome and Genetics in the Development of Gastrointestinal Disease

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