Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice
Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice
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DOI：
10.1038/s41598-020-63627-y
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发表时间：
2020-04-15
影响因子：
4.6
通讯作者：
Miyoshi, Noriyuki
中科院分区：
文献类型：
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作者：
Sanada, Shunsuke;Suzuki, Takuji;Miyoshi, Noriyuki
宿主和肠道菌群相互作用和影响以维持体内平衡和触发病理过程是至关重要的。最近的研究表明，将小鼠肠道内容物移植到无菌小鼠受体中，可以传播供体的表型，例如与生活方式相关的疾病相关的低水平慢性炎症。这些发现表明肠道细菌产生一些分子来触发病理信号。然而，诱导肥胖和II型糖尿病表型的粪便微生物代谢物尚未完全阐明。在这里，我们发现肠道细菌代谢物stercobilin（一种粪便色素）诱导小鼠巨噬细胞RAW264细胞的促炎活性，包括tnf - α和IL-1 β诱导。ob/ob小鼠粪便中促炎stercobilin水平显著高于对照C57BL/6 J小鼠。此外，在本研究中，我们首次在小鼠血浆中检测到stercobilin， ob/ob小鼠的stercobilin水平高于C57BL/6 J小鼠。因此，stercobilin可能被重吸收，通过血液系统循环，并有助于ob/ob小鼠的低水平慢性炎症。由于stercobilin是一种生物活性代谢物，它可能是一种潜在的有前途的诊断生物标志物。进一步的分析，阐明stercobilin的代谢率和重吸收机制，可能提供可能的治疗和预防靶点。
It is crucial that the host and intestinal microflora interact and influence each other to maintain homeostasis and trigger pathological processes. Recent studies have shown that transplantation of the murine intestinal content to recipient germ-free mice enables transmission of the donor's phenotypes, such as low level chronic inflammation associated with lifestyle-related diseases. These findings indicate that intestinal bacteria produce some molecules to trigger pathological signals. However, fecal microbial metabolites that induce obesity and the type II diabetic phenotype have not been fully clarified. Here, we showed that the intestinal bacterial metabolite stercobilin, a pigment of feces, induced proinflammatory activities including TNF-alpha and IL-1 beta induction in mouse macrophage RAW264 cells. Proinflammatory stercobilin levels were significantly higher in ob/ob mice feces than in the feces of control C57BL/6 J mice. Moreover, in this study, we detected stercobilin in mice plasma for the first time, and the levels were higher in ob/ob mice than that of C57BL/6 J mice. Therefore, stercobilin is potentially reabsorbed, circulated through the blood system, and contributes to low level chronic inflammation in ob/ob mice. Since, stercobilin is a bioactive metabolite, it could be a potentially promising biomarker for diagnosis. Further analyses to elucidate the metabolic rate and the reabsorption mechanism of stercobilin may provide possible therapeutic and preventive targets.