Inflammatory bowel diseases · 2024
Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Liu Moting, Zhang Yao, Liu Jia, Xiang Caigui, Lu Qiukai, Lu Huimin, Yang Tao, Wang Xiaohan, Zhang Qingli, Fan Chen, Feng Chunlan, Zou Duowu, Li Heng, Tang Wei
Аннотация
BACKGROUND: Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation.
METHODS: Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms.
RESULTS: In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6.
CONCLUSIONS: In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.
METHODS: Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms.
RESULTS: In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6.
CONCLUSIONS: In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.