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PSYCHOPHARMACOLOGY · 2021 ·Vol. 238 ·期 11 ·3131-3142 · IF 4.53

Pivotal role of the gut microbiota in congenital insensitivity to pain with anhidrosis

Zhang Mi,Hong Yishun,Wu Wenyao,Li Ningbo,Liu Baowen,Sun Jiaoli,Cao Xueqin,Ye Ting,Zhou Ling,Liu Cunming,Yang Chun,Zhang Xianwei

Background Increasing evidence has shown that the occurrence and development of various human diseases are closely related to the gut microbiota. We compared the gut microbial communities of human subjects with congenital insensitivity to pain with anhidrosis (CIPA) and healthy controls (HCs) to assess whether fecal microbiota transplantation (FMT) into germ-free mice and mice in acute pain influenced the behaviors of the host. Methods We utilized 16 s rRNA analysis to compare the gut microbial communities of CIPA subjects and HCs and assessed whether FMT into germ-free mice and mice in acute pain influenced the behaviors of the host. Results In a 16 s RNA analysis, the CIPA group had significant decreases in the relative abundance of 11 bacteria, whereas 7 bacteria were significantly increased. In further animal experiments, the transplantation of fecal samples from CIPA patients to healthy mice significantly increased their scores on both the mechanical withdrawal test and the tail flick test; in an acute plantar incision model, scores were also significantly increased on the mechanical withdrawal test at 4 and 5 days after the operation. Moreover, pseudo-germ-free mice receiving fecal bacteria from patients with CIPA took significantly longer to escape and had a significantly longer path length on training days 1, 2, and 5 and also had fewer platform crossings and spent less time in the target quadrant in the probe trial. Conclusions Our results suggest that the gut microbiota in CIPA subjects plays a key role in behaviors. Therapeutic strategies for improving the gut microbiota might alleviate CIPA symptoms.

研究领域: 微生物学 · 神经科学 · 转化医学
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Microbiology Spectrum · 2024 · IF 3.7

Interplay between gut microbiota and tryptophan metabolism in type 2 diabetic mice treated with metformin

Yvhao Xie,Xinxin Li,Qingshi Meng,Jinjun Li,Xin Wang,Liying Zhu,Weiwei Wang,Xiaoqiong Li

Tryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (R2 > 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of Dubosiella, Turicibacter, RF39, Clostridia_UCG-014, and Alistipes. Spearman’s correlation analysis revealed positive correlations between Turicibacter and Alistipes with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.

研究领域: 药理学 · 微生物学 · 代谢组学 · 糖尿病研究 · 分子生物学
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Food & Function · 2022 ·Vol. 13 ·期 13 ·7274-7286 · IF 6.317

Tracking the gastrointestinal digestive and metabolic behaviour of Dendrobium officinale polysaccharides by fluorescent labelling

Zhijing Wu,Yu Zhang,Gang Nie,Junxi Liu,Hao Mei,Zihao He,Pengfei Dou,Kaiping Wang

Recently, Dendrobium officinale polysaccharide (DOP), a typical acetylated glucomannan, has been widely applied in functional foods owing to its excellent bioactivity. However, the insufficiency of studies on in vivo process severely limits the further utilization of DOP. The aim of this study was to systematically investigate the gastrointestinal digestive behaviour of DOP after oral administration by labelling it with two fluorescein aminopyrene-1,3,6-trisulfonic acids, trisodium salt (APTS) and cyanine 7.5 (Cy7.5). Combining the results of NIR imaging and HPGPC, we found that DOP was poorly absorbed directly in the prototype form; instead, DOP moved with the intestinal contents to the distal part of the intestine, where Bacteroides aggregated for a prolonged time and was metabolized to oligosaccharide-like substances. In contrast, the digestive degradation of DOP in pseudo-sterile mice with a targeted clearance of Bacteroides significantly weakened, which provided the basis and direction for the subsequent search for more specific metabolic pathways of DOP in vivo.

CAS / MDL: 114-07-8 13292-46-1
研究领域: 食品科学 · 营养学 · 微生物学 · 药理学
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Chinese Journal of Natural Medicines · 2023 · IF 4.6

Tripterygium hypoglaucum extract ameliorates adjuvant-induced arthritis in mice through the gut microbiota

Jianghui HU,Jimin NI,Junping ZHENG,Yanlei GUO,Yong YANG,Cheng YE,Xiongjie SUN,Hui XIA,Yanju LIU,Hongtao LIU

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium , Akkermansia , and Lactobacillus and the decreases of Butyricimonas , Parabacteroides , and Anaeroplasma . Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.

CAS / MDL: 443-48-1
研究领域: 药理学 · 免疫学 · 微生物学 · 风湿病学
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