The role of the gut microbiota in the pathology and prevention of liver disease

Several microorganisms belonging to the intestinal microbiota act in an ecosystem responsible for maintaining the homeostasis and vital functions of human beings. From birth to old age the diversity of the intestinal microbiota may change due to environmental factors such as nutrition, immunity, diseases or the use of antibiotics leading to dysbiosis. Improvement in microbiota diversity can be achieved by modifying related risk factors through changes in lifestyle and a healthy diet. Besides, the addition of probiotics, prebiotics or the combination of both (symbiotics), can result in the improvement of the intestinal permeability, inflammatory pathways and the immune system. Also, the use of probiotics prevents harmful bacteria and their derived products (e.g., bacteriocins, endotoxins, hydrogen sulfide, etc.) to leak through the intestinal wall to the circulation that results in the activation of signaling pathways that may be implicated in liver disease. The liver receives a constant flow of noxious entities that promote inflammation and oxidative stress. The use of probiotics with clinical evidence in liver disease, represent a novel therapeutic alternative, inducing positive changes in the balance of the intestinal microbiota which lead to improvement in liver function tests (AST and ALT), decreasing tumor necrosis factor-α (TNF-α), andblood cholesterol, among other risk factors. In this review, we discuss the main elements that play a leading role in the development of steatosis as well as the benefits of using probiotics and the impact in the quality of life of patients that develop cirrhosis.     

益生菌以及益生元在肥胖及其代谢综合征中的潜在作用

肥胖以及相关的代谢综合征已经成为全球性的公共健康问题。大量的研究表明,肥胖形成以及减肥过程均与肠道菌群密切相关且相互影响。肠道菌群以及弱炎症反应成为肥胖以及相关代谢综合征的两大重要影响因素。本文综述了近几年来,肠道菌群失调对宿主能量储存以及新陈代谢的影响,以及弱炎症反应对肥胖引起的代谢综合征的影响。大量的研究证明,益生元有助于益生菌的生长,而益生菌可以调节肠道菌群以及改善肠道内弱炎症反应,借助于益生菌以及益生元的方法也许能为由肠道菌群失调以及弱炎症反应引起的肥胖及其代谢综合征提供一种新的治疗方法。     

Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease

Inflammatory bowel disease (IBD) is a result of chronic inflammation caused, in some part, by dysbiosis of intestinal microbiota, mainly commensal bacteria. Gut dysbiosis can be caused by multiple factors, including abnormal immune responses which might be related to genetic susceptibility, infection, western dietary habits, and administration of antibiotics. Consequently, the disease itself is characterized as having multiple causes, etiologies, and severities. Recent studies have identified >200 IBD risk loci in the host. It has been postulated that gut microbiota interact with these risk loci resulting in dysbiosis, and this subsequently leads to the development of IBD. Typical gut microbiota in IBD patients are characterized with decrease in species richness and many of the commensal, and beneficial, fecal bacteria such as Firmicutes and Bacteroidetes and an increase or bloom of Proteobacteria. However, at this time, cause and effect relationships have not been rigorously established. While treatments of IBD usually includes medications such as corticosteroids, 5-aminosalicylates, antibiotics, immunomodulators, and anti-TNF agents, restoration of gut dysbiosis seems to be a safer and more sustainable approach. Bacteriotherapies (now called microbiota therapies) and dietary interventions are effective way to modulate gut microbiota. In this review, we summarize factors involved in IBD and studies attempted to treat IBD with probiotics. We also discuss the potential use of microbiota therapies as one promising approach in treating IBD. As therapies based on the modulation of gut microbiota becomes more common, future studies should include individual gut microbiota differences to develop personalized therapy for IBD.     

Intestinal microbiota in human health and disease: the impact of probiotics

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis.     

后生元(postbiotics):调节肝硬化患者肠道菌群及疾病进程的新策略

肝硬化是慢性肝炎发展的终末阶段,患者出现有不同程度的肠道菌群失调,并伴有肠道屏障功能的缺失和菌群移位,是引发肝硬化并发症的重要原因。尽管益生菌能在多个层面保护肠道屏障功能,但其在肝硬化肠道菌群紊乱中的疗效并不明确。现在的研究发现一些益生菌的组分或代谢产物有着与益生活菌类似的益生功效,包括稳定肠道菌群、加强肠上皮屏障功能和调节肠黏膜免疫反应等,其重要的优点是具有明确的分子结构和显著的生物活性,可能是未来调节肝硬化肠道菌群及疾病进程的新方向。本文主要总结了肝硬化肠道菌群失调对于肝硬化并发症及疾病进程的影响,探讨了益生菌的作用及局限性,并重点讨论后生元在调控肝硬化肠道菌群及疾病进程中的应用前景。     

肠道菌群与高尿酸血症及痛风的相关性研究

高尿酸血症以及痛风的发病率持续升高,已经成为一个重大的公共卫生问题。肠道菌群的结构改变或失调可引起机体代谢紊乱,肠道微生态尤其与代谢性疾病的发生发展关系密切。目前研究发现高尿酸血症、痛风患者存在肠道菌群失调,降尿酸治疗后肠道菌群可发生相应改变,并且益生菌制剂具有降尿酸作用。本文概述高尿酸血症及痛风患者的肠道菌群特点,从高嘌呤及高果糖饮食对肠道菌群的影响、肠道参与嘌呤和尿酸的代谢、代谢性内毒素血症以及痛风相关炎症因子等方面探讨肠道菌群与高尿酸血症及痛风的关系,并展望肠道菌群可能成为未来诊治高尿酸血症以及痛风的一种新方法。     

Cervicovaginal microbiome dynamics after taking oral probiotics

The vaginal microbiota is less complex than the gut microbiota, and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health. Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population. In this study, 60 Chinese women were followed for over a year before, during, and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina. Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis. The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year, which was not affected by probiotic intake, whereas in the dysbiosis group, the microbiota was more diverse and changed markedly over time. Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics,indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis, providing opportunities for targeted and personalized microbiome reconstitution.     

Probiotics – do they have a role in the pig industry?

The delivery of certain living microorganisms in food has long been suggested as having positive health effects in humans. This practice has extended into food animal production, with a variety of microorganisms being used; lactic acid bacteria, various Bacillus species and the yeast Saccharomyces cerevisiae have been particularly used in the pig industry. The increased interest in probiotics is essentially due to the problem of microbial resistance to antibiotics and following the ban of the use of antibiotics in animal production, probiotics being considered an alternative means to reduce pathogen infection and improve animal health especially around the time of weaning. However, there is still a need to clarify the probiotic effectiveness in pigs, and the underlying mechanisms. When assessing the efficacy of probiotics one must consider the particular strain of organism being used and the production stage of the pigs being treated. The reproducible delivery of probiotics in industrial pig production is problematic as maintenance of viability is key to their beneficial activity, but difficult to achieve with commonly used feed processing technologies. One specific context where probiotics organisms may be reliably delivered is in systems utilising fermented liquid feeds. Liquid feed may be fermented by the activity of wild lactic acid bacteria or may be stimulated using specific isolates as 'starters'; the latter system has advantages in terms of reproducibility and speed of fermentation. The farm context in which the organism is used is likely to be critical; the use of probiotics is more likely to result in measurable economic gains in animals living in sub-optimal conditions rather than in those reared in the highest welfare and husbandry conditions. The establishment of a beneficial lactic acid bacteria population at birth may lead to healthier animals, this may be most effectively achieved by treating sows, which provide an amplification step and flood the neonatal pigs' environment with desirable bacterial strains. In contrast, it may be sufficient to provide a supportive, protective microbiota around the time of weaning as this is a time of major crisis with instability and loss of certain bacterial populations.     

Antibiotics as growth promotants: mode of action

Recent concerns about the use of growth-promoting antibiotics in pig diets have renewed interest in the immunologic and growth-regulating functions of the gastrointestinal (GI) tract. The numerically dense and metabolically active microbiota ofthe pig GI tract represents a key focal point for such questions. The intestinal microbiota is viewed typically as a beneficial entity for the host. Intestinal bacteria provide both nutritional and defensive functions for their host. However, the host animal invests substantially in defensive efforts to first sequester gut microbes away from the epithelial surface, and second to quickly mount immune responses against those organisms that breach epithelial defenses. The impact of host responses to gut bacteria and their metabolic activities require special consideration when viewed in the context of pig production in which efficiency of animal growth is a primary objective. Here, we summarize the working hypothesis that antibiotics improve the efficiency of animal growth via their inhibition of the normal microbiota, leading to increased nutrient utilization and a reduction in the maintenance costs ofthe GI system. In addition, novel molecular ecology techniques are described that can serve as tools to uncover the relationship between intestinal microbiology and growth efficiency.     

肠道菌群在肺纤维化疾病中的调节作用

肺纤维化是一种以成纤维细胞增殖及大量细胞外基质及胶原聚集,并伴随炎症损伤为特征的呼吸系统疾病终末期改变。该疾病以肺功能障碍和呼吸衰竭为主要病理基础,发病率逐年上升,目前治疗方法有限。在肠肺之间的功能调控研究中,肠道菌群构成变化引起的机体微生态失调能够通过多种方式影响呼吸系统疾病的进程。本文聚焦于肺纤维化等肺部疾病的肠肺调控研究前沿领域,综述了多种肺纤维化疾病的致病机制、肠道菌群的功能、肠肺双向调节和益生菌群干预治疗等方面的最新进展。此外,本文也提出了该领域目前存在的问题,以期为今后的调控机制探索和治疗药物研发提供有力的理论支持及策略支撑。     

Probiotics L. acidophilus and B. clausii Modulate Gut Microbiota in Th1- and Th2-Biased Mice to Ameliorate Salmonella Typhimurium-Induced Diarrhea

Gut microbiota play important role in maintaining health. Probiotics are believed to augment it further. We aimed at comparing effects of probiotics, Lactobacillus acidophilus (LA) and Bacillus clausii (BC) (a) on the gut microbiota abundance and diversity and (b) their contributions to control intestinal dysbiosis and inflammation in Th1- and Th2-biased mice following Salmonella infection. We report how could gut microbiota and the differential immune bias (Th1 or Th2) of the host regulate host responses when challenged with Salmonella typhimurium in the presence and absence of either of the probiotics. LA was found to be effective in ameliorating the microbial dysbiosis and inflammation caused by Salmonella infection, in Th1 (C57BL/6) and Th2 (BALB/c)-biased mouse. BC was able to ameliorate Salmonella-induced dysbiosis and inflammation in Th2 but not in Th1-biased mouse. These results may support probiotics LA as a treatment option in the case of Salmonella infection.

     

肠道微生物群加重黑腹果蝇盐胁迫反应

【背景】高盐饮食目前引起普遍关注,肠道微生物与盐胁迫的相互作用正成为研究热点之一。【目的】以黑腹果蝇为宿主模型,探讨肠道微生物对果蝇盐胁迫反应的影响与潜在机理。【方法】利用平板计数法和定量PCR法检测果蝇肠道载菌量;利用存活率和运动能力测定装置测定果蝇适合度;用化学试剂和抗生素处理建立无菌果蝇,测定肠道菌对果蝇盐胁迫反应的影响;利用亮蓝食用色素染料渗透性实验检测果蝇肠道屏障的完整性;应用实时定量PCR检测先天免疫系统的活性。【结果】高盐处理引起果蝇肠道菌群失调,导致其肠道载菌量显著增加。此外,高盐饮食(high salt diet,HSD)降低了黑腹果蝇成虫的存活率和运动能力。经0.75 mol/L NaCl处理,雌性GF (germ-free)果蝇存活率比对照组升高了11%,同时混合抗生素有效地提高了高盐处理后果蝇的存活率。肠道微生物加剧了肠道屏障功能损伤,雌性GF果蝇出现染料渗透性实验现象的百分率比对照组降低了8%。在分子水平上,盐胁迫下雌性GF果蝇体内Attacin-C、Duox基因表达水平分别是CR(conventionally reared)果蝇的2.5倍和1.7倍。【结论】肠道微生物加重果蝇盐胁迫反应,引发高盐诱导的肠屏障功能紊乱,并且抑制高盐诱导的先天免疫活性。     

Effects of feed additives on the development on the ileal bacterial community of the broiler chicken

Intensifying concerns about the use of antimicrobials in meat and poultry production has enhanced interest in the application of prebiotics, probiotics and enzymes to enhance growth and prevent disease in food animals. Growth-promoting antibiotics enhance growth of animals by reducing the load of bacteria in the intestine, by reducing colonization by intestinal pathogens or by enhancing the growth and/or metabolism of beneficial bacteria in the intestine. Recently, molecular ecology, utilizing DNA-sequence heterogeneity of the 16S rRNA gene, has revealed a surprising diversity of uncharacterized bacteria inhabiting this ecosystem. We used this approach to determine the effect of growth-promoting antibiotics on the development and composition of the ileal bacterial community. Pairwise comparisons, correspondence analysis and community diversity indices revealed significant differences among the treatments (bacitracin/virginiamycin or monensin) and controls. Antibiotics reduced the diversity of the ileal bacterial community and induced communities rich in Clostridia throughout the life of the broiler chicken. These results indicate that some bacterial species, such as lactobacilli, were suppressed and also suggest that many intestinal Clostridia may be non-pathogenic. Future studies should focus on characterizing the important bacterial species needed to stabilize the intestinal microbiota and identifying those commensals that stimulate and enhance development of intestinal function.     

Selecting, testing and understanding probiotic microorganisms

The interest in probiotics and the modulation of microbiota for restoring and maintaining health continues to gain momentum. Research is fueled by a need to develop alternatives to antibiotics and drugs that have severe side effects. It is recognised that bacteria play a major role in human and animal health, and how scientific advances help to explain how and when probiotics work. This minireview provides an update on critical studies, particularly since 2002, that are helping to explain the mechanisms of action of probiotic organisms.     

Intestinal microbiota associated with differential feed conversion efficiency in chickens

Analysis of model systems, for example in mice, has shown that the microbiota in the gastrointestinal tract can play an important role in the efficiency of energy extraction from diets. The study reported here aimed to determine whether there are correlations between gastrointestinal tract microbiota population structure and energy use in chickens. Efficiency in converting food into muscle mass has a significant impact on the intensive animal production industries, where feed represents the major portion of production costs. Despite extensive breeding and selection efforts, there are still large differences in the growth performance of animals fed identical diets and reared under the same conditions. Variability in growth performance presents management difficulties and causes economic loss. An understanding of possible microbiota drivers of these differences has potentially important benefits for industry. In this study, differences in cecal and jejunal microbiota between broiler chickens with extreme feed conversion capabilities were analysed in order to identify candidate bacteria that may influence growth performance. The jejunal microbiota was largely dominated by lactobacilli (over 99% of jejunal sequences) and showed no difference between the birds with high and low feed conversion ratios. The cecal microbial community displayed higher diversity, and 24 unclassified bacterial species were found to be significantly (<0.05) differentially abundant between high and low performing birds. Such differentially abundant bacteria represent target populations that could potentially be modified with prebiotics and probiotics in order to improve animal growth performance.     

Effect of dietary modulation of intestinal microbiota on reproduction and early growth

An optimal balance of intestinal microbiota is necessary for digestive and immune health. Poor performance, susceptibility to infections, and decreased growth rate can be signs of an imbalanced microbiome. Dietary strategies to establish and maintain an optimal balance of microbiota include prebiotics (food for indigenous microbiota in the gastrointestinal tract) and probiotics (beneficial microbiota consumed by the animal). Recent research regarding use of probiotics and prebiotics in reproducing and growing livestock and companion animals is summarized. Documented benefits include prevention of diarrhea, decreased mortality, establishment of a healthy microbiota balance, and improved immune function.     

肠道菌群与腹泻型肠易激综合征 相关性的研究进展

肠易激综合征(IBS)是一种常见的功能性胃肠道疾病,其特征是反复发作的腹痛,伴随排便频率与大便性状的改变。腹泻为主的肠易激综合征(IBS-D)是其主要亚型,主要表现是腹痛和腹泻。目前IBS-D的发病机制尚不完全明确,但大量的研究提示可能与胃肠道动力紊乱、黏膜通透性和肠上皮屏障功能改变、内脏高敏感性增加、"脑-肠-菌"轴失调、肠道感染与炎症反应激活、精神心理因素异常等有关。随着研究的不断深入,发现肠道菌群与IBS-D的关系密切,调节肠道菌群的益生菌干预成为缓解IBS-D相关症状的手段之一。本研究就近十余年来肠道菌群情况与IBS-D关系的研究现状作一综述。     

Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics

The intestinal microbiota is now recognised to play key roles in health due to its involvement in many aspects of human physiology. Disturbance in gut microbiota (dysbiosis) is thus associated with many diseases including nonalcoholic fatty liver disease (NAFLD) which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis. The mechanisms for the effect of dysbiosis in NAFLD pathogenesis are not completely elucidated. Many explanations have been proposed to trigger dysbiosis, leading to NAFLD including inflammation, ethanol produced by the gut bacteria and lipotoxicity. Recently the roles of bile acids and nuclear receptors are highly regarded. It is well known that gut microbes produce enzymes that convert primary bile acids into secondary bile acids in the intestines. Several studies have demonstrated that disturbance of the intestinal microbiota leads to decreased synthesis of secondary bile acids, which in turn decreases activation of nuclear receptors such as farnesoid X receptor (FXR), pregnane X receptor, Takeda G-protein–coupled bile acid protein 5 and vitamin D receptor. These receptors are important in energy regulation and their dysregulation can cause NAFLD. Therefore, stimulation of nuclear receptors especially FXR has been extensively explored for the amelioration of NAFLD. However, paradoxical effects of nuclear receptor activation are a major problem for the clinical application of nuclear receptor stimuli. We further posit that microbiome restoration could be an alternative approach for the treatment of NAFLD. Several gut bacteria are now known to be involved in bile acid metabolism. It will be necessary to identify which one/ones is/are feasible. Careful selection of commensal bacteria for probiotics may lead to an effective therapy for NAFLD.     

婴幼儿期使用抗生素所致菌群失衡 对疾病发生的影响研究进展

人体表面定植的各种细菌承载庞大的基因库,它们之间的互相作用对维持人体微生态的稳定必不可少。婴幼儿期是生长发育的重要时期,同样也是菌群演替的关键时期。此时期免疫系统发育尚未成熟,容易受病毒及细菌感染,而使用抗生素治疗细菌感染是难以避免的。然而抗生素的使用不仅改变正常菌群,进而改变人体的免疫反应和代谢模式,同时对人体产生长远的影响,导致疾病的发生,甚至引起人体定植的正常菌群产生耐药性,构成新的耐药菌株的来源。本文就近年来婴幼儿期使用抗生素所致菌群失衡对疾病发生的影响作一综述。     

Obesity and microbiota: an example of an intricate relationship

It is widely accepted that metabolic disorders, such as obesity, are closely linked to lifestyle and diet. Recently, the central role played by the intestinal microbiota in human metabolism and in progression of metabolic disorders has become evident. In this context, animal studies and human trials have demonstrated that alterations of the intestinal microbiota towards enhanced energy harvest is a characteristic of the obese phenotype. Many publications, involving both animal studies and clinical trials, have reported on the successful exploitation of probiotics and prebiotics to treat obesity. However, the molecular mechanisms underlying these observed anti-obesity effects of probiotics and prebiotic therapies are still obscure. The aim of this mini-review is to discuss the intricate relationship of various factors, including diet, gut microbiota, and host genetics, that are believed to impact on the development of obesity, and to understand how modulation of the gut microbiota with dietary intervention may alleviate obesity-associated symptoms.