Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice.
Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice.
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DOI：
10.1038/s41598-021-00088-x
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发表时间：
2021-10-14
影响因子：
4.6
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Jang HM;Kim JK;Joo MK;Shin YJ;Lee CK;Kim HJ;Kim DH
肠道菌群失调与炎症性肠病（IBD）和精神疾病的发生密切相关。在此，为了解伴有（IBD/D +）或不伴有抑郁症（IBD/D -）的IBD患者之间肠道微生物群组成和生理效应的差异，我们分析了伴有（/D +）或不伴有抑郁症（/D -）的IBD患者以及健康志愿者（HV）的粪便微生物群组成，并研究了这些粪便微生物群移植（FMT）对小鼠全身炎症和焦虑/抑郁发生的影响。来自IBD/D +或IBD/D -患者的FMT在移植小鼠中引发了类似IBD的结肠炎：它们增加了结肠中的髓过氧化物酶活性、白细胞介素 - 1β和白细胞介素 - 6的表达以及NF - κB⁺/CD11c⁺细胞数量。IBD/D +患者粪便（IBD/D + - F）的移植比IBD/D - - F更强烈地引发类似IBD的结肠炎。来自IBD/D +患者的FMT还导致了类似焦虑/抑郁的行为，增加了海马体中NF - κB⁺/Iba1⁺和脂多糖（LPS）⁺/Iba1⁺细胞数量，并减少了BDNF⁺/NeuN⁺细胞数量。它们增加了血液中的LPS水平。来自IBD/D -患者的FMT导致了类似焦虑的行为，但没有导致类似抑郁的行为。IBD - F中肠道微生物群的α - /β - 多样性和组成与HV粪便（HV - F）不同。肠杆菌科和肠球菌科的数量以及LPS水平在IBD - F中高于HV - F。肠球菌科数量在IBD/D + - F中高于IBD/D - - F。然而，将HV - F移植到先前移植了IBD/D + - F的小鼠中，显著减少了类似抑郁的行为、海马体中NF - κB⁺/Iba1⁺和LPS⁺/Iba1⁺细胞数量、粪便和血液中的LPS水平以及结肠中的白细胞介素 - 1β表达。这些发现表明，在IBD患者中，抑郁/焦虑的发作可能依赖于肠道菌群失调导致细菌LPS过度产生和紧密连接蛋白表达受抑制所引起的肠道渗漏相关的全身炎症。
Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D−), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D−) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D− caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D−-F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D− caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D−-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.
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影响因子：
4.6
作者：
Jang HM;Lee KE;Lee HJ;Kim DH
通讯作者：
Kim DH
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通讯作者：
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