Microbial metabolism of dietary phenolic compounds in the colon

Plant foods contain substantial amounts of phenolic compounds. Dietary interventions with phenolic supplementation show that phenolic compounds are transformed into phenolic acids or lactone structures by intestinal microbiota. The colon is the main site of microbial fermentation. The metabolites circulate in plasma and are excreted via urine. The entero-hepatic circulation ensures that their residence time in plasma is extended compared to that of their parent compounds. Thus these metabolites may exert systemic effects, which however have not been studied adequately. In particular the health implications of microbial metabolites of flavonoids, mostly phenolic acids, are unknown. This review aims to elucidate the microbial metabolism of most of the phenolic classes: flavonoids, isoflavonoids, lignans, phenolic acids and tannins. Some examples of biological activity studies of flavonoid and lignan metabolites are given. Biological significance of enterolactone, a mammalian plant lignan metabolite, has been studied quite extensively, but convincing evidence of the health benefits of the diverse pool of microbial metabolites is still scarce. Hopefully, novel tools in systems biology and the constant search for biomarkers will elucidate the role of the phenolic metabolome in health and in the prevention of chronic diseases. In conclusion, the colon is not only an excretion route, but also an active site of metabolism and deserves further attention from the scientific community.     

The intestinal microbiome associated with lipid metabolism and obesity in humans and animals

Intestinal microbiota is considered to play an integral role in maintaining health of host by modulating several physiological functions including nutrition, metabolism and immunity. Accumulated data from human and animal studies indicate that intestinal microbes can affect lipid metabolism in host through various direct and indirect biological mechanisms. These mechanisms include the production of various signalling molecules by the intestinal microbiome, which exert a strong effect on lipid metabolism, bile secretion in the liver, reverse transport of cholesterol and energy expenditure and insulin sensitivity in peripheral tissues. This review discusses the findings of recent studies suggesting an emerging role of intestinal microbiota and its metabolites in regulating lipid metabolism and the association of intestinal microbiota with obesity. Additionally, we discuss the controversies and challenges in this research area. However, intestinal micro-organisms are also affected by some external factors, which in turn influence the regulation of microbial lipid metabolism. Therefore, we also discuss the effects of probiotics, prebiotics, diet structure, exercise and other factors on intestinal microbiological changes and lipid metabolism regulation.     

Endocrine organs of cardiovascular diseases: Gut microbiota

Gut microbiota (GM) is a collection of bacteria, fungi, archaea, viruses and protozoa, etc. They inhabit human intestines and play an essential role in human health and disease. Close information exchange between the intestinal microbes and the host performs a vital role in digestion, immune defence, nervous system regulation, especially metabolism, maintaining a delicate balance between itself and the human host. Studies have shown that the composition of GM and its metabolites are firmly related to the occurrence of various diseases. More and more researchers have demonstrated that the intestinal microbiota is a virtual ‘organ’ with endocrine function and the bioactive metabolites produced by it can affect the physiological role of the host. With deepening researches in recent years, clinical data indicated that the GM has a significant effect on the occurrence and development of cardiovascular diseases (CVD). This article systematically elaborated the relationship between metabolites of GM and its effects, the relationship between intestinal dysbacteriosis and cardiovascular risk factors, coronary heart disease, myocardial infarction, heart failure and hypertension and the possible pathogenic mechanisms. Regulating the GM is supposed to be a potential new therapeutic target for CVD.     

The interplay between host cellular and gut microbial metabolism in NAFLD development and prevention

Metabolism regulation centred on insulin resistance is increasingly important in nonalcoholic fatty liver disease (NAFLD). This review focuses on the interactions between the host cellular and gut microbial metabolism during the development of NAFLD. The cellular metabolism of essential nutrients, such as glucose, lipids and amino acids, is reconstructed with inflammation, immune mechanisms and oxidative stress, and these alterations modify the intestinal, hepatic and systemic environments, and regulate the composition and activity of gut microbes. Microbial metabolites, such as short-chain fatty acids, secondary bile acids, protein fermentation products, choline and ethanol and bacterial toxicants, such as lipopolysaccharides, peptidoglycans and bacterial DNA, play vital roles in NAFLD. The microbe–metabolite relationship is crucial for the modulation of intestinal microbial composition and metabolic activity. The intestinal microbiota and their metabolites participate in epithelial cell metabolism via a series of cell receptors and signalling pathways and remodel the metabolism of various cells in the liver via the gut–liver axis. Microbial metabolic manipulation is a promising strategy for NAFLD prevention, but larger-sampled clinical trials are required for future application.     

The role of short-chain fatty acids in the interplay between diet,gut microbiota,and host energy metabolism

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.     

银杏双黄酮和银杏内酯B与人体肠道菌群体外互作研究

【目的】银杏提取物在防治心血管系统和神经系统疾病方面发挥重要功能。鉴于肠道菌群已被认定为一个新兴的药物作用靶标,研究银杏双黄酮和银杏内酯与人体肠道菌群之间的相互作用具有非常重要的意义,这将为进一步理解银杏提取物的功能和作用机制奠定基础。【方法】本研究使用人体肠道菌群体外批量发酵、细菌总量测定、细菌16S rDNA高通量测序、气相色谱和液相色谱检测等方法,对银杏双黄酮和银杏内酯B单独或复合在体外与人体肠道菌群的相互作用进行研究。【结果】银杏双黄酮和银杏内酯B单独添加对人体肠道菌群总量、肠道菌群结构组成和短链脂肪酸产量没有显著影响。但有意思的是,复合添加银杏双黄酮和银杏内酯B后,Coriobacteriaceae科和Cupriavidus属细菌的比例显著升高,Gemella菌细菌比例显著降低。功能基因预测分析发现,编码K00076、K12143、K07716和K00220的基因在复合添加银杏双黄酮和银杏内酯B后显著富集。K00076和K00220是氧化还原酶,催化CH-OH供体基团的电子转移,可能参与银杏双黄酮和银杏内酯B的代谢和修饰。HPLC检测发现,人体肠道菌群体外对银杏双黄酮和银杏内脂B的降解修饰率分别为70%和35%左右。【结论】体外复合添加银杏双黄酮和银杏内酯B可显著改变肠道某些细菌的丰度。同时,体外研究表明肠道菌群具有代谢修饰银杏双黄酮和银杏内酯B的功能。     

Clostridium,Bacteroides and Prevotella associates with increased fecal metabolites Trans-4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE)

PurposeTo investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E).Patients and methods(1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without M. tuberculosis (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy.ResultsMtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family Veillonellacea and Bateroidaceae and their genera Veillonella and Bacteroides significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut Clostridium, Bacteroides and Prevotella was closely related to the change of fecal metabolites such as Trans-4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy.ConclusionAnti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12088-022-01003-2.     

The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury

Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient''s systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.     

粪菌移植研究的文献计量学和可视化分析

【背景】粪菌移植是近年医学领域研究的热点,不但能够治疗消化系统疾病,而且在神经及精神系统、心血管系统相关疾病的治疗中均有不错的疗效,有着广阔的应用前景。【目的】掌握国内外粪菌移植的研究现状、热点及发展趋势,为相关领域科研工作者的研究提供参考。【方法】基于Web of Science核心数据库,通过CiteSpace对2011-2021年的年度发文量、作者、国家、期刊、被引情况和关键词等进行可视化分析。【结果】筛选后共纳入4 905篇文献,目前全球粪菌移植研究的文献数量呈快速增长趋势;美国和中国是发文量最多的国家。中国学者的总发文量虽然位居世界第二,但中心度和篇均被引频次较低,说明受关注程度及学术影响力不足,在发文质量上还有待提高;Gastroenterology是国内外学者发文量最多的期刊,Frontiers in Microbiology是中国学者发文量最多的期刊;粪菌移植呈现出多学科交叉的发展特点;粪菌移植目前的研究热点主要与肠内疾病(炎症性肠病、艰难梭菌感染)和肠外疾病(如抑郁、冠状动脉粥样硬化等)有关;粪菌移植在未成年人中的应用、对胰岛素敏感度的影响、测序技术在肠道菌群的应用及...     

Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice

The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.     

Total glycosides from stems of Cistanche tubulosa alleviate depression-like behaviors: bidirectional interaction of the phytochemicals and gut microbiota

BackgroundAs the most frequently used kidney-yang tonifying herb in traditional Chinese medicine, dried succulent stems of Cistanche tubulosa (Schenk) Wight (CT) have been shown to be effective in the treatment of depression. However, the antidepressant components and their underlying mechanism remain unclear.PurposeTo explore the active components of CT against depression, as well as the potential mechanisms.Study design and methodsBehavioral despair tests were used to assess the antidepressant activities of polysaccharides, oligosaccharides and different glycoside-enriched fractions separated from CT, as well as the typical gut microbiota metabolites including 3-hydroxyphenylpropionic acid (3-HPP) and hydroxytyrosol (HT). Furthermore, the effects of bioactive fractions and metabolites on chronic unpredictable mild stress (CUMS) model were explored with multiple pharmacodynamics and biochemical analyses. Changes in colonic histology and the intestinal barrier were observed by staining and immunohistochemical analysis. Gut microbial features and tryptophan-kynurenine metabolism were explored using 16S rRNA sequencing and western-blotting, respectively.ResultsTotal glycosides (TG) dramatically alleviated depression-like behaviors compared to different separated fractions, reflecting in the synergistic effects of phenylethanoid and iridoid glycosides on the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, severe neuro- and peripheral inflammation, and deficiencies in 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor in the hippocampus. Moreover, TG mitigated low-grade inflammation in the colon and intestinal barrier disruption, and the abundances of several bacterial genera highly correlated with the HPA axis and inflammation in CUMS rats. Consistently, the expression of indoleamine 2, 3-dioxygenase 1 (IDO1) in the colon was significantly reduced after TG administration, accompanied by the suppression of tryptophan-kynurenine metabolism. On the other hand, HT also exerted a marked antidepressant effect by ameliorating HPA axis function, pro-inflammatory cytokine release, and tryptophan-kynurenine metabolism, while it was unable to largely adjust the disordered gut microbiota in the same manner as TG. Surprisingly, superior to fluoxetine, TG and HT could further improve dysfunction of the hypothalamic-pituitary-gonadal axis and abnormal cyclic nucleotide metabolism.ConclusionTG are primarily responsible for the antidepressant activity of CT; its effect might be achieved through the bidirectional interaction of the phytochemicals and gut microbiota, and reflect the advantage of CT in the treatment of depression.     

Pharmacokinetics and metabolism of dietary flavonoids in humans

Flavonoids are components of fruit and vegetables that may be beneficial in the prevention of disease such as cancer and cardiovascular diseases. Their beneficial effects will be dependent upon their uptake and disposition in tissues and cells. The metabolism and pharmacokinetics of flavonoids has been an area of active research in the last decade. To date, approximately 100 studies have reported the pharmacokinetics of individual flavonoids in healthy volunteers. The data indicate considerable differences among the different types of dietary flavonoids so that the most abundant flavonoids in the diet do not necessarily produce the highest concentration of flavonoids or their metabolites in vivo. Small intestinal absorption ranges from 0 to 60% of the dose and elimination half-lives (T_1/2) range from 2 to 28 h. Absorbed flavonoids undergo extensive first-pass Phase II metabolism in the small intestine epithelial cells and in the liver. Metabolites conjugated with methyl, glucuronate and sulfate groups are the predominant forms present in plasma. This review summarizes the key differences in absorption, metabolism and pharmacokinetics between the major flavonoids present in the diet. For each flavonoid, the specific metabolites that have been identified so far in vivo are indicated. These data should be considered in the design and interpretation of studies investigating the mechanisms and potential health effects of flavonoids.     

江山乌猪肠道黏膜菌群组成及其功能的性别差异

肠道黏膜微生物在调控宿主生理功能方面发挥重要作用,其结构组成受到多种因素影响。性别被认为是塑造肠道微生物的因素之一。然而,性别对肠道黏膜菌群的差异影响还不清楚。【目的】以江山乌猪为研究对象,探究性别差异对其肠道黏膜微生物组成及功能的影响。【方法】选取性成熟的雌性和雄性江山乌猪各8头,利用16S rRNA基因高通量测序技术分析回肠和结肠黏膜菌群。【结果】在回肠黏膜中,雄性江山乌猪菌群的Chao1指数和Shannon指数显著高于雌性(P<0.05),在结肠黏膜中,不同性别江山乌猪菌群Chao1指数和Shannon指数无显著差异(P>0.05)。菌群差异分析显示,回肠黏膜中,沙雷氏菌属(Serratia)和埃希氏志贺菌属(Escherichia_Shigella)在雌性组中的相对丰度显著高于雄性组(P<0.05),雄性组中Oscillospiraceae UCG-005、拟普雷沃氏菌属(Alloprevotella)、布劳特氏菌属(Blautia)和Prevotellaceae_NK3B31_group相对丰度显著高于雌性组(P<0.05);结肠黏膜中,雌性组中unclassified_Muribaculaceae、Rikenellaceae_RC9_gut_group和Prevotellaceae UCG-003相对丰度显著高于雄性组(P<0.05),Oscillospiraceae UCG-005、Lachnospiraceae_NK4A136_group和unclassified_Lachnospiraceae在雄性组中相对丰度更高(P<0.05)。功能预测发现,雄性乌猪回肠黏膜菌群显著富集了氨基酸代谢、碳水化合物代谢和能量代谢等功能途径(P<0.05);结肠黏膜菌群主要富集了膜转运相关的ABC转运蛋白和信号转导相关的双组分系统等功能途径(P<0.05)。【结论】不同性别江山乌猪肠黏膜菌群结构及功能具有明显差异。这些结果揭示了不同性别江山乌猪肠道黏膜菌群的差异特征,为了解和挖掘我国地方畜禽品种肠道微生物资源提供部分参考。     

肠道菌群在中药代谢中的作用

近年来,中药在疾病防治方面所发挥的巨大作用受到了广泛认可。科学合理地解释中药的作用机制将有助于提高其利用价值。越来越多的证据表明肠道菌群在中药治疗中起着至关重要的作用,是打开我国中医药宝库的一把钥匙。肠道菌群在中药代谢过程中发挥着复杂的作用:一方面,人类肠道菌群通过编码多种活性酶,促进了中药组分中的非碳水化合物小分子与碳水化合物在肠道中的代谢过程;另一方面,经肠道菌群代谢转化后产生的中药产物具有多种药理作用。因此,在未来中药研究中应更多地考虑肠道微生态因素,这有助于为中药的药理作用机制研究奠定新的科学基础。     

A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice

This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.     

A commentary on methodological aspects of hydrolysable tannins metabolism in ruminant: a perspective view

Although, the application of tannic acid (TA), gallic acid (GA), natural hydrolysable tannins (HT)-rich ingredients, and HT-rich feeds in ruminant feeding have been explored in order to modify or manipulate microbial activities of digestive tract of animals, the interaction between HT and gastrointestinal microbiota and the fate of HT metabolites (GA, ellagic acid, pyrogallol, resorcinol, phloroglucinol, catechol and urolithin) derived from gastrointestinal microbial HT metabolism in the animal as a whole and animal products are missing. Incomplete biotransformation of HT and TA to GA, pyrogallol, resorcinol, phloroglucinol and other phenolic metabolites is a prevalent phenomenon discovered by researchers who examine the fate of HT metabolites in ruminant. While the rest of fellow researchers do not even examine the fate of HT metabolites and assume the complete biotransformation and fermentation of HT metabolites to volatile fatty acids (VFA). Only three studies have successfully identified the complete biotransformation and fermentation of HT metabolites to VFA in ruminant. The HT metabolites, mostly pyrogallol, produced through incomplete biotransformation of HT have adverse effects on gastrointestinal microbiota and host animal. Lack of awareness regarding the metabolism of HT metabolites and its consequences would compromise ruminant gastrointestinal microbiota, animal welfare, our environment and the power of research papers’ findings. In this perspective paper, I will bring to attention a new angle on the biotransformation and fermentation of HT metabolites in gastrointestinal tract, the role of gastrointestinal microbiota and deficiency of current approach in isolating tannin-degrading bacteria from rumen. Also, suggestions for better monitoring and understanding HT metabolisms in ruminant are presented.     

肠道菌群：肠道干细胞增殖分化的调节者

肠道干细胞(intestinal stem cells, ISCs)是肠道各类上皮细胞的来源,通过平衡增殖与分化维持肠道稳态。同时,肠道菌群及其代谢物在维持宿主肠道稳态中也发挥着重要作用。随着技术的发展,研究者认识到ISCs与肠道菌群之间存在相互作用。研究表明,ISCs对上皮细胞亚型的调控影响肠道菌群的组成,并且肠道菌群及其代谢物也影响ISCs介导的上皮发育。本文阐述了ISCs分化对肠道菌群的影响,重点总结了肠道菌群及其代谢物调控ISCs增殖分化的研究进展,从菌群调控ISCs的角度探讨肠道损伤的治疗思路,并对未来可能的研究方向进行讨论。     

肠道菌群-肠-脑-肌轴信号交流的研究进展

肠道菌群及其代谢产物在老年神经退行性疾病、胃肠道疾病以及肌肉骨骼系统性疾病的发病与康复中的作用越来越受到关注。肠道菌群及其代谢产物可通过免疫、内分泌和神经系统等多种途径调节大脑神经或肌肉骨骼系统功能;反之,肠道、大脑或肌肉骨骼系统也可通过炎症、代谢或线粒体通路作用于肠道系统,调节肠道菌群微生态,形成肠道菌群与肠-脑、肠-肌、 肠-脑-肌之间的双向信号交流机制,从而影响机体健康。因此,本综述总结了肠道菌群如何通过代谢产物、肠道通透性和免疫-神经通路建立起肠-脑-肌之间的相互联系,为促进大脑神经的可塑性和改善肌肉健康提供新思路。     

Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.     

Protective effects of flavonoids and two metabolites against oxidative stress in neuronal PC12 cells

AimsRecent interest has focused on plant antioxidants as potentially useful neuroprotective agents. In most studies only the genuine forms of flavonoids were used, although they are rapidly metabolized. Therefore, we have compared protective activities of two flavonoids (luteolin, quercetin) and two of their bioavailable metabolites (3,4-DHPAA and 3,4-DHT) against oxidative stress, induced by peroxides (t-BHP, H₂O₂) and iron (FeSO₄), in neuronal PC12 cells.Main methodsWe have measured their effect on the prevention of cell death (MTT assay), glutathione depletion (GSH assay), lipid peroxidation (MDA assay) and production of ROS (DCF assay). Differentiated PC12 cells were used as a model system of neuronal cells. The compounds (concentration range 6–25 µmol/L) were tested in preincubation and coincubation experiments.Key findingsIn MTT and DCF assays all tested compounds showed excellent protection. When cells were exposed to peroxides, both metabolites increased GSH levels less efficiently than their parent flavonoids in both types of incubations. Following exposure to iron, only coincubation significantly prevented GSH depletion and the metabolites surprisingly mimicked the suppressive effect of flavonoids. MDA levels induced by all stressors were reduced more potently during coincubation than during preincubation with polyphenols. While the lipophilic metabolite 3,4-DHT exerted excellent antilipoperoxidant activity, the hydrophilic metabolite 3,4-DHPAA was less effective.SignificanceThese results demonstrate that most of the protective effects of flavonoids against oxidative stress in PC12 cells are continued despite biodegradation of the parent flavonoids. In general, the lipophilic metabolite 3,4-DHT was more active than the hydrophilic 3,4-DHPAA.