Oral Sub-Chronic Ochratoxin a Exposure Induces Gut Microbiota Alterations in Mice

Gut microbiota plays crucial roles in maintaining host health. External factors, such as diet, medicines, and environmental toxins, influence the composition of gut microbiota. Ochratoxin A (OTA) is one of the most prevalent and relevant mycotoxins and is a highly abundant food and animal feed contaminant. In the present study, we aimed to investigate OTA gut microbiome toxicity in mice sub-chronically exposed to low doses of OTA (0.21, 0.5, and 1.5 mg/kg body weight) by daily oral gavage for 28 days. Fecal microbiota from control and OTA-treated mice was analyzed using 16S ribosomal RNA (rRNA) gene sequencing followed by metagenomics. OTA exposure caused marked changes in gut microbial community structure, including the decrease in the diversity of fecal microbiota and the relative abundance of Firmicutes, as well as the increase in the relative abundance of Bacteroidetes at the phylum level. At the family level, six bacterial families (unclassified Bacteroidales, Porphyromonadaceae, unclassified Cyanobacteria, Streptococcaceae, Enterobacteriaceae, Ruminococcaceae) were significantly altered by OTA exposure. Interestingly, OTA-induced changes were observed in the lower-dose OTA groups, while high-dose OTA group microbiota was similar to control group. Our results demonstrated that sub-chronic exposure at low doses of OTA alters the structure and diversity of the gut microbial community.     

The antidepressant-like effect of probiotics and their faecal abundance may be modulated by the cohabiting gut microbiota in rats

Numerous studies have been published describing the effect of various probiotics (PRO) on behaviours related to psychiatric disease. We have previously shown a robust antidepressant-like effect of PRO in rats, but over time, the treatment effect seems to vary significantly between different sets of rats from the same commercial vendor. Therefore, we hypothesised that the antidepressant-like response may be modulated by the cohabiting gut microbiota.The aims of the present study were (1) to investigate any differences in the gut microbiota composition between responders (Resp) and non-responders (Non-resp) to PRO with regards to depressive-like behaviour, and (2) to evaluate the effects of PRO on the microbiota composition.Two sets of 20 male Sprague-Dawley rats each were treated with multi-species PRO (nine Bifidobacterium, Lactococcus and Lactobacillus species) for eight weeks and subjected to a behavioural assessment. Faecal samples were collected for 16?s rRNA (VR4) gene amplicon sequencing (Illumina MiSeq).As previously reported, PRO-treated Resp animals showed a marked decrease in depressive-like behaviour, whereas no such response was seen in Non-resp. We observed profound differences in the gut microbiota composition between the two sets of rats, and the relative faecal abundance of the genera that comprised PRO was higher in Resp than in Non-resp although treated with the same dose of PRO. Particularly, the relative abundance of the Lactobacillus genus was not increased in PRO-treated Non-resp animals.In conclusion, the cohabiting microbiota and the faecal abundance of PRO may modulate the antidepressant-like effect of PRO in rats.     

胆汁酸-肠道菌群轴在2型糖尿病中的作用

目的 分析2型糖尿病(type 2 diabetes mellitus,T2DM)患者和正常人群胆汁酸与肠道菌群差异,探讨胆汁酸-肠道菌群轴在T2DM中的作用。方法 利用代谢组学、16S rRNA测序手段分别对T2DM患者中的血清胆汁酸含量及粪便肠道微生物进行检测及分析,结合斯皮尔曼相关性分析,明确胆汁酸-肠道菌群在T2DM中的代谢对话关系。结果 血清胆汁酸含量和肠道微生物的丰度在T2DM患者与正常人群中存在一定的差异。与正常人群相比,甘氨熊脱氧胆酸、牛磺鹅脱氧胆酸、甘氨鹅脱氧胆酸的含量在T2DM患者中显著降低;T2DM患者中肺炎克雷伯菌属、普拉梭菌属的相对丰度较正常人群明显升高,而狄氏副拟杆菌属、普雷沃菌属、艾克曼菌属、双歧杆菌属的相对丰度明显降低;斯皮尔曼相关性分析表明甘氨熊脱氧胆酸与狄氏副拟杆菌属、艾克曼菌属呈正相关,与克雷伯氏菌属呈负相关。结论 胆汁酸-肠道菌群轴是维持机体稳态的必要因素,在T2DM中发挥重要作用。     

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)‐induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500 μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154 days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue‐associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high‐dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high‐dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin‐33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin‐3, granulocyte‐macrophage colony‐stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.     

Impacts of earthworm introduction and cadmium on microbial communities composition and function in soil

Heavy metal contamination of soil has become a public concern. Earthworms are key players in the functioning and service of soil ecosystems, with comprehension of their introduction in the polluted soil offering new insights into the protection of soil resources. In the present study, we evaluated the effects of earthworm (Eisenia fetida) introduction and Cd (0, 10, 30, and 60 mg kg⁻¹ of Cd) exposure upon soil microbial community using 16S rRNA gene amplicon sequencing. Our research demonstrated that Gemmatimonadetes and Deinococcus-Thermus upregulated significantly, while Chryseolinea showed an obvious decreasing trend after earthworm introduction. In Cd contaminated soil, many genera exhibited a greater presence of Cd-dependent bacteria, namely Cd-tolerant bacteria such as Altererythrobacter and Luteimonas, and a decrease of sensitive bacteria, such as Amaricoccus and Haliangium. Moreover, functional prediction analysis of soil microbiota indicated that earthworm introduction and Cd exposure changed functional pathways of soil microorganisms. The results obtained in this study are beneficial for understanding soil microbial community impacted by earthworm, and for exploring Cd resistant or tolerant bacteria, with potentially significant findings for soil biodiversity and Cd bioremediation.     

Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut–kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine–p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut–kidney axis.     

乌梅丸对肥胖小鼠肠道菌群结构的影响

目的： 探讨乌梅丸对肥胖小鼠肠道菌群结构的影响。方法： 利用高通量基因测序技术,对正常对照组小鼠、高脂饮食诱导的模型组肥胖小鼠和乌梅丸干预后的肥胖小鼠的粪便样本进行16SrRNA测序,比较分析各组小鼠肠道菌群结构的差异,并用PICRUSt软件预测差异功能通路。结果： 乌梅丸干预后,肥胖小鼠的体质量显著下降,白色脂肪细胞体积减小,白色脂肪纤维化程度减轻;同时肠道菌群结构发生显著改变,乌梅丸不仅改变了肥胖小鼠肠道多样性,使其趋近于正常对照组小鼠,还在门、属、种3个水平上显著改变了肥胖小鼠的肠道细菌分布比例,使肥胖小鼠肠道内4个菌门、9个菌属、4个菌种的丰度趋近于正常对照组小鼠肠道丰度水平,肠道益生菌（多形拟杆菌、Parabacteroides_goldsteinii、狄氏副拟杆菌）丰度显著上升,且能降低厚壁菌门与拟杆菌门比例。此外上述肠道菌群的改变可引起卟啉与叶绿素代谢、二甲苯退化、D-精氨酸和D-鸟氨酸代谢、苯甲酸降解、生物膜形成-霍乱弧菌、RNA转运、类黄酮生物合成7个通路功能的改变。结论： 乌梅丸可以治疗小鼠肥胖症,改变肥胖小鼠肠道菌群结构。     

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs) have been involved in the pathogenesis of obesity and insulin resistance. However, evidence relating berberine(BBR), gut microbiota, BCAAs, and insulin resistance is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet(NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales; families Streptococcaceae, Clostridiaceae, and Prevotellaceae; and genera Streptococcus and Prevotella. Compared with the HFD group, predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment. Accordingly, the elevated serum BCAAs of HFD group were significantly decreased by BBR. Furthermore, the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by activation of the multienzyme branched-chain α-ketoacid dehydrogenase complex, whereas by inhibition of the phosphorylation state of BCKDHA(E1α subunit) and branched-chain α-ketoacid dehydrogenase kinase. The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3 T3-L1 adipocytes. Finally, data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs. Besides, functional microbiomics integrated high-throughput microbial genomics, metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.     

高通量测序技术分析喂养不耐受早产儿肠道菌群的动态变化

目的:了解喂养不耐受(FI)早产儿肠道菌群的动态变化。方法:选取2017年1-7月徐州医科大学附属徐州市妇幼保健院新生儿科收治的56例喂养不耐受早产儿,入院后常规应用广谱青霉素,发生喂养不耐受时给予小剂量红霉素促进胃肠动力治疗。采集患儿生后首次胎便(FI1组)、出现喂养不耐受时的粪便(FI2组)、喂养不耐受消失后的粪便(FI3组),采用高通量测序技术对粪便样本中所有细菌进行16S rRNA测序,比较各组菌群的多样性及丰度变化。结果:与FI1组相比,FI2组的Shannon、Ace指数均下降,克雷伯杆菌丰度升高,拟杆菌、双歧杆菌、乳酸杆菌、罗尔斯通菌、红球菌的丰度降低(P均<0.05)。FI3组与FI2组的Shannon、Ace指数及克雷伯杆菌、双歧杆菌、乳酸杆菌、红球菌丰度比较差异均无统计学意义(P均>0.05),FI3组的拟杆菌、罗尔斯通菌丰度继续降低(P均<0.05)。结论:早产儿喂养不耐受发生时,肠道菌群的多样性及丰度明显降低,克雷伯杆菌丰度升高,拟杆菌、双歧杆菌、乳酸杆菌、罗尔斯通菌、红球菌的丰度降低。     

益生菌益生元复合制剂对头孢曲松引起的肠道菌群及免疫异常改善效果的研究

摘要：目的 探究由乳双歧杆菌HN019、乳双歧杆菌V9与益生元共同组成的益生菌、益生元复合制剂对头孢曲松引起的 小鼠免疫异常以及肠道菌群失调的改善效果。方法 45只四周龄雄性Balb/c小鼠随机分为3组,分别灌胃生理盐水、头孢曲松以 及头孢曲松+益生菌复合制剂30d后,检测受试小鼠的体重、逆转录实时荧光定量PCR(RT-qPCR)分析脾脏细胞中免疫細胞因子的 mRNA表达、用RT-qPCR和高通量测序技術检测粪便双歧杆菌含量以及粪便细菌的构成。结果 头孢曲松+复合制剂组受试小鼠 体重显著低于空白组(P<0.05)。头孢曲松组脾脏IL-10 mRNA表达量有下降趋势,头孢曲松+益生菌复合制剂组受试小鼠脾脏IL- 10 mRNA表达量显著高于头孢曲松组(P<0.05)。头孢曲松组受试小鼠粪便双歧杆菌含量有下降趋势,头孢曲松+益生菌复合制剂 组受试小鼠粪便双歧杆菌含量显著高于头孢曲松组(P<0.05)。头孢曲松组和头孢曲松+复合制剂组与空白组相比,受试小鼠α-多 样性有不同程度的降低。头孢曲松组拟杆菌门减少,厚壁菌门和肠球菌属增多。头孢曲松+复合制剂组与头孢曲松组相比,受 试小鼠厚壁菌门与肠球菌属的相对丰度减少,放线菌门增加。结论 头孢曲松可导致宿主免疫功能异常,肠道双歧杆菌等有益 菌减少,肠道菌群整体结构紊乱。益生菌、益生元复合制剂可通过促进抗炎因子的产生改善了宿主免疫功能,并通过增加双歧 杆菌和减少某些致病菌在一定程度上改善了头孢曲松导致的宿主肠道菌群异常、促进肠道健康。     

Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. Flavobacterium, Myroides, Corynebacterium, Alcaligenaceae, Oligella and other conditional pathogens increased significantly in the model group, while Blautia and Roseburia, the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, i.e., urease, could assist the treatment and prevention of this disease.     

降脂方对非酒精性脂肪肝的治疗效果及其对患者肠道菌群和代谢的影响

目的 考察降脂方对非酒精性脂肪肝(non-alcoholic fatty liver disease，NAFLD)的治疗效果及其对肠道菌群和代谢的影响。方法 选取NAFLD患者13例作为患者组，选取体检健康志愿者15名作为健康组，患者组服用降脂方3月后，通过患者糖脂代谢、胰岛和肝脏功能的变化考察降脂方的治疗效果，通过16S rRNA测序技术考察粪便标本肠道菌群丰度的变化，代谢组学技术考察粪便标本代谢产物含量的变化。结果 NAFLD患者肠道菌群构成发生较大变化，多样性显著下降(P<0.05)，巨单胞菌属占优势，服药3月后，降脂方可显著降低NAFLD患者肝脏硬度并改善其糖脂代谢、胰岛和肝脏功能，肠道中布劳特氏菌属相对丰度显著上调(P<0.05)，栖粪杆菌属、布劳特氏菌属和拟杆菌属较占优势。与降脂方治疗前组相比，治疗后组患者粪便中代谢产物68个显著上调，43个显著下调(P均<0.05)，嘧啶代谢等功能具有统计学意义(P<0.05)。结论 降脂方对NAFLD具有较好的治疗效果，可调控NAFLD患者肠道菌群和代谢功能。     

Mycotoxin and Gut Microbiota Interactions

The interactions between mycotoxins and gut microbiota were discovered early in animals and explained part of the differences in susceptibility to mycotoxins among species. Isolation of microbes present in the gut responsible for biotransformation of mycotoxins into less toxic metabolites and for binding mycotoxins led to the development of probiotics, enzymes, and cell extracts that are used to prevent mycotoxin toxicity in animals. More recently, bioactivation of mycotoxins into toxic compounds, notably through the hydrolysis of masked mycotoxins, revealed that the health benefits of the effect of the gut microbiota on mycotoxins can vary strongly depending on the mycotoxin and the microbe concerned. Interactions between mycotoxins and gut microbiota can also be observed through the effect of mycotoxins on the gut microbiota. Changes of gut microbiota secondary to mycotoxin exposure may be the consequence of the antimicrobial properties of mycotoxins or the toxic effect of mycotoxins on epithelial and immune cells in the gut, and liberation of antimicrobial peptides by these cells. Whatever the mechanism involved, exposure to mycotoxins leads to changes in the gut microbiota composition at the phylum, genus, and species level. These changes can lead to disruption of the gut barrier function and bacterial translocation. Changes in the gut microbiota composition can also modulate the toxicity of toxic compounds, such as bacterial toxins and of mycotoxins themselves. A last consequence for health of the change in the gut microbiota secondary to exposure to mycotoxins is suspected through variations observed in the amount and composition of the volatile fatty acids and sphingolipids that are normally present in the digesta, and that can contribute to the occurrence of chronic diseases in human. The purpose of this work is to review what is known about mycotoxin and gut microbiota interactions, the mechanisms involved in these interactions, and their practical application, and to identify knowledge gaps and future research needs.     

Morphological changes in the avian intestine induced by citrinin and lack of effect of aflatoxin and T-2 toxin as seen with scanning electron microscopy

D. R. Witlock, R. D. Wyatt and M. D. Ruff. Morphological changes in the avian intestine induced by citrinin and lack of effect of aflatoxin and T-2 toxin as seen with scanning electron microscopy. Toxicon15, 41–44, 1977.—Young broiler chickens (Gallus domesticus) fed 250 or 500 μg of citrinin per g of ration exhibited changes in morphology of the midgut compared with control birds fed a ration with no citrinin. These changes included: (1) a ‘herringbone’-like pattern due to marked interdigation of the villi, (2) continuous villar ridges which were oriented around the gut lumen, and (3) the fusion of the villi into convoluted ribbon forms. The duodenum and ileum were relatively unaffected when compared to control tissue. Although aflatoxin and T-2 toxin exert severe physiological effects in the chick, no changes in villous architecture in any gut region were observed.     

Modifications of gut microbiota are associated with the severity of IgA nephropathy in the Chinese population

Immunoglobulin A nephropathy (IgAN) is a common glomerular disease. The pathogenesis of IgAN is associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a role in IgAN remains unclear. Blood and faecal samples were collected from 52 patients with IgAN and 25 healthy controls (HCs). The gut microbiome was analysed using the 16S ribosomal RNA gene. The levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor α (TNF-α), interleukin-1, and C-reactive protein were quantified. Substantial differences in the gut microbiota were identified between patients with IgAN and HCs (P < 0.05). Bacteroides and Escherichia-Shigella levels were significantly higher in patients with IgAN than in HCs, while Bifidobacterium and Blautia spp. Levels were lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in patients with IgAN with high urine RBC count (≥10/HP) and proteinuria (≥1 g/24 h) levels. Correlation analysis was used to assess the association between gut microbiota and biomarkers in patients with IgAN. The results showed that Prevotella 7 levels were negatively correlated with Gd-IgA1, LBP, sCD14, ICAM-1, and TNF-α levels, while Bifidobacterium spp. Levels presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella levels were negatively correlated with Prevotella 7. In patients with IgAN, gut modifications were characterised by an increase in the number of pathogenic bacteria and a reduction in the levels of beneficial bacteria, suggesting that the disturbance of intestinal microflora might be important in the severity of IgAN.     

Host microbiota dictates the proinflammatory impact of LPS in the murine liver

Gut microbiota can impact liver disease development via the gut-liver axis. Liver inflammation is a shared pathological event in various liver diseases and gut microbiota might influence this pathological process. In this study, we studied the influence of gut microbiota on the inflammatory response of the liver to lipopolysaccharide (LPS). The inflammatory response to LPS (1–10 μg/ml) of livers of specific-pathogen-free (SPF) or germ-free (GF) mice was evaluated ex vivo, using precision-cut liver slices (PCLS). LPS induced a more pronounced inflammatory response in GF PCLS than in SPF PCLS. Baseline TNF-α gene expression was significantly higher in GF slices as compared to SPF slices. LPS treatment induced TNF-α, IL-1β, IL-6 and iNOS expression in both SPF and GF PCLS, but the increase was more intense in GF slices. The anti-inflammatory markers SOCS3 and IRAK-M gene expression was significantly higher in GF PCLS than SPF PCLS at 24h with 1 µg/ml LPS treatment, and IL-10 was not differently expressed in GF PCLS than SPF PCLS. In addition, TLR-4 mRNA, but not protein, at basal level was higher in GF slices than in SPF slices. Taken together, this study shows that, in mice, the host microbiota attenuates the pro-inflammatory impact of LPS in the liver, indicating a positive role of the gut microbiota on the immune homeostasis of the liver.     

Carboxymethyl chitosan perturbs inflammation profile and colonic microbiota balance in mice

Carboxymethyl chitosan (CMC) is widely used in food and medicine as a biodegradable polymer. However, its effects on inflammation profile and colon health are not well investigated. In the present study, CMC was given to mice to evaluate its possible effects on body weight, blood glucose level, inflammation factors, intestinal permeability and colon microbiota. Results showed that blood glucose level of CMC treated mice was relatively higher than control ones. Glucose tolerance test revealed that CMC treated mice presented higher peak glucose level and lower lag level. CMC treatment increased serum LDL-c level, decreased serum HDL-c and IL-10 level in the fat tissue. Moreover, CMC treatment downregulated the expression of tight junction protein, occludin and ZO-1, in colon as evaluated by Western blot. Colon microbiota analysis demonstrated that CMC treatment significantly decreased the OTUs and relative species abundance. The level of Enterobacteriaceae, Lachnospiraceae and several other bacteria were much higher in the colon content of CMC treated mice. The results collectively suggest that CMC treatment induces disturbance of glucose and fat metabolism, affects the inflammation profile, perturbs colon microbiota balance.     

肠道菌群相关的抗抑郁治疗研究进展

目的 介绍肠道菌群与抑郁症的病理机制以及相关治疗的研究进展,为后续以肠道菌为靶点的抗抑郁药物的研发提供帮助。方法 查阅近年来肠道菌群与抑郁症方面的33篇中英文文献进行分类总结,从肠道菌群的门、科、属水平的角度探讨了抑郁状态下肠道菌群多样性的变化,从分子水平上阐述了肠道菌与抑郁症发病机制之间的关系,总结现有相关研究,进一步探索以肠道菌群为靶点进行药物研发治疗的可行性。结果 肠道菌紊乱与抑郁症之间相互作用,现有益生菌等生物制剂可通过改善肠道菌群病理状态下的紊乱对抑郁症治疗起到缓解作用。结论 肠道菌群失调与抑郁的发生密切相关,以肠道菌为靶点的相关药物研发治疗,可能成为治疗抑郁症的新途径。     

参苓白术散对伴焦虑腹泻型肠易激综合征模型小鼠的改善作用及机制

目的:研究参苓白术散对伴焦虑腹泻型肠易激综合征(IBS-D)模型小鼠的改善作用,并从肠道微生态角度初步阐明其作用机制。方法:将C57 BL/6小鼠随机分为空白对照组、模型组、参苓白术散组(3.6 g/kg),每组8只。除空白对照组外,模型组和参苓白术散组小鼠以皮下注射皮质酮联合灌胃番泻叶水煎液及慢性束缚建立伴焦虑IBS-D模型。造模成功后,空白对照组、模型组小鼠灌胃给予生理盐水,参苓白术散组灌胃给予相应药物,连续给药4周。末次给药后,检测各组小鼠的稀便率、腹泻指数、体质量、糖水偏好百分比、穿过旷场中心区域次数、最小疼痛阈值和海马组织中内源性脑神经营养因子(BDNF)及血清中5-羟色氨(5-HT)的水平;提取各组小鼠盲肠内容物进行微生物DNA提取并测序,采用Alpha、Beta多样性分析法分析肠道微生物丰度及多样性。结果:与空白对照组比较,模型组小鼠体质量、糖水偏好百分比、穿过旷场中心区域次数、最小疼痛阈值、海马组织中BDNF水平和肠道中厚壁菌门微生物的相对丰度及Lachnospiraceae_NK4A136_group属微生物的相对丰度均显著降低(P<0.05);稀便率、腹泻指数、血清中5-HT水平和疣微菌门微生物的相对丰度、艾克曼菌属微生物的相对丰度均显著升高(P<0.05);肠道微生物种类差异较大。与模型组比较,参苓白术散组小鼠体质量、糖水偏好百分比、穿中心区域次数、最小疼痛阈值、海马组织中BDNF水平和肠道中厚壁菌门微生物的相对丰度、Lachnospiraceae_NK4A136_group属微生物的相对丰度均显著升高(P<0.05或P<0.01);稀便率、腹泻指数、血清中5-HT水平、疣微菌门微生物的相对丰度、艾克曼菌属微生物的相对丰度均显著降低(P<0.05);肠道微生物种类差异较大。结论:参苓白术散可改善伴焦虑IBS-D模型小鼠的腹泻和焦虑行为,升高其海马组织中BDNF水平,降低血清中5-HT水平;其作用机制可能与降低肠道微生物疣微菌门、艾克曼菌属微生物的相对丰度,升高厚壁菌门、Lachnospiraceae_NK4A136_group属微生物的相对丰度有关。     

谷氨酰胺胃肠外营养对急性放射性肠炎大鼠肠屏障功能的影响

目的探讨谷氨酰胺胃肠外营养对急性放射性肠炎大鼠肠屏障功能的作用。方法SD大鼠行全腹部60Coγ射线8Gy放射后,实验动物随机分为三组,常规全成分胃肠外营养组(Standard totalparenteral nutrition,STD组,n=10):大鼠输入常规静脉营养液;谷氨酰胺组(Glutamine-enriched totalparenteral nutrition,GLN组,n=10):大鼠输入附加谷氨酰胺的静脉营养液;正常组(n=10)为未经腹部照射的正常大鼠,连续7d全成分胃肠外营养。采用光镜、电镜观察、结合图像分析系统和无菌采取肠系膜淋巴结做细菌培养。结果GLN组小肠蛋白质和DNA的含量明显高于STD组,GLN组空、回肠绒毛高度、隐窝深度、黏膜厚度、全层壁厚度均显著大于STD组。扫描电镜的观察结果:GLN组和STD组小肠绒毛顶部都有程度不同的糜烂形成,但GLN组绒毛表面糜烂较少,而STD组则较多。GLN组肠系膜淋巴结细菌移位率明显低于STD组。结论附加丙氨酰-GLN二肽的全成分胃肠外营养能有效的保护肠黏膜辐射性损伤后肠屏障功能和防止肠细菌移位。