具减肥功效的益生菌研究进展

摘要：肥胖症患病率在全球范围内持续增长,其中导致肥胖的最主要因素是能量摄入和消耗失衡。肠道菌群是涉及肥胖和代谢紊乱的环境因素,肥胖动物和人类患者表现出了肠道菌群组成和结构的改变。这种菌群失衡能影响机体能量平衡、炎症和肠道屏障功能等,进而影响代谢。研究显示益生菌可有效改善高脂饮食造成的肥胖。改变肠道菌群可能会成为预防或控制肥胖的有效疗法,该领域尚处于早期阶段,相关数据仍有限。本综述旨在总结最新的具有减肥功效益生菌的实验研究,帮助了解减肥益生菌的最新进展,为该领域后续研究提供帮助。     

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。     

The art of targeting gut microbiota for tackling human obesity

Recently, a great deal of interest has been expressed regarding strategies to tackle worldwide obesity because of its accelerated wide spread accompanied with numerous negative effects on health and high costs. Obesity has been traditionally associated with an imbalance in energy consumed when compared to energy expenditure. However, growing evidence suggests a less simplistic event in which gut microbiota plays a key role. Obesity, in terms of microbiota, is a complicated disequilibrium that presents many unclear complications. Despite this, there is special interest in characterizing compositionally and functionally the obese gut microbiota with the help of in vitro, animal and human studies. Considering the gut microbiota as a factor contributing to human obesity represents a tool of great therapeutic potential. This paper reviews the use of antimicrobials, probiotics, fecal microbial therapy, prebiotics and diet to manipulate obesity through the human gut microbiota and reveals inconsistencies and implications for future study.     

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。     

Nutritional modulation of gut microbiota — the impact on metabolic disease pathophysiology

The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host–microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction.     

Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease?

Obesity is now considered a major public health concern globally as it predisposes to a number of chronic human diseases. Most developed countries have experienced a dramatic and significant rise in obesity since the 1980s, with obesity apparently accompanying, hand in hand, the adoption of "Western"-style diets and low-energy expenditure lifestyles around the world. Recent studies report an aberrant gut microbiota in obese subjects and that gut microbial metabolic activities, especially carbohydrate fermentation and bile acid metabolism, can impact on a number of mammalian physiological functions linked to obesity. The aim of this review is to present the evidence for a characteristic "obese-type" gut microbiota and to discuss studies linking microbial metabolic activities with mammalian regulation of lipid and glucose metabolism, thermogenesis, satiety, and chronic systemic inflammation. We focus in particular on short-chain fatty acids (SCFA) produced upon fiber fermentation in the colon. Although SCFA are reported to be elevated in the feces of obese individuals, they are also, in contradiction, identified as key metabolic regulators of the physiological checks and controls mammals rely upon to regulate energy metabolism. Most studies suggest that the gut microbiota differs in composition between lean and obese individuals and that diet, especially the high-fat low-fiber Western-style diet, dramatically impacts on the gut microbiota. There is currently no consensus as to whether the gut microbiota plays a causative role in obesity or is modulated in response to the obese state itself or the diet in obesity. Further studies, especially on the regulatory role of SCFA in human energy homeostasis, are needed to clarify the physiological consequences of an "obese-style" microbiota and any putative dietary modulation of associated disease risk.     

Liraglutide modulates gut microbiota and reduces NAFLD in obese mice

Metabolic disorders such as insulin resistance and diabetes are associated with obesity and nonalcoholic fatty liver disease (NAFLD). The aggressive form of a fatty liver disease may progress to cirrhosis and hepatocellular carcinoma. Furthermore, recent studies demonstrated that there is a dysbiosis in the gut microbiota associated with early stages of metabolic disease. Therefore, the identification and repurposing of drugs already used to treat insulin resistance may be an excellent option for other disorders. We evaluated the effect of liraglutide on obesity, NAFLD and gut microbiota modulation in two different animal models of obesity: the ob/ob mice and the high-fat diet (HFD)-fed mice. Liraglutide treatment induced significant weight loss in both obesity models, showed improvements in glycemic parameters and reduced inflammatory cell infiltration in the cecum and the liver. In ob/ob mice, the liraglutide treatment was able to reduce the accumulation of liver fat by 78% and reversed steatosis in the HFD mice. The gut microbiota analysis showed that liraglutide changed the overall composition as well as the relative abundance of weight-relevant phylotypes such as a reduction of Proteobacteria and an increase of Akkermansia muciniphila in the treated HFD group. We show that liraglutide can lead to weight loss and gut microbiota modulations, and is associated with an improvement of NAFLD. Furthermore, by generating a profile of the intestinal microbiota, we compiled a list of potential bacterial targets that may modulate metabolism and induce a metabolic profile that is considered normal or clinically controlled.     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.     

Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice

Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance.     

基于代谢组学的植物多酚及其肠道健康效应研究进展

综述了植物多酚的分类和来源、在代谢组学技术的驱动下,新型多酚物质的鉴定、控制植物多酚合成途径的关键因子以及多酚的功能特性的研究进展,阐述了植物多酚在肠道中的代谢以及其作为“益生元”调节肠道微生态并影响机体健康的重要功能。目前的研究表明不同植物多酚在调节肠道微生态方面存在差异,多数有促进肠道有益菌作用,并通过与肠道微生物“互作”发挥促进健康效应。总之,植物多酚作为“益生元”影响人体健康可能离不开肠道微生物的介导。各个植物多酚的益生功能也需要进一步阐析,在此过程中需要考虑宿主,膳食等混杂因素的综合影响,且需要拓展临床应用方面的研究。     

Putative Mechanisms Underlying the Beneficial Effects of Polyphenols in Murine Models of Metabolic Disorders in Relation to Gut Microbiota

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders.     

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.     

Anti-obesity effects of gut microbiota are associated with lactic acid bacteria

The prevalence of obesity is rapidly becoming endemic in industrialized countries and continues to increase in developing countries worldwide. Obesity predisposes people to an increased risk of developing metabolic syndrome. Recent studies have described an association between obesity and certain gut microbiota, suggesting that gut microbiota might play a critical role in the development of obesity. Although probiotics have many beneficial health effects in humans and animals, attention has only recently been drawn to manipulating the gut microbiota, such as lactic acid bacteria (LAB), to influence the development of obesity. In this review, we first describe the causes of obesity, including the genetic and environmental factors. We then describe the relationship between the gut microbiota and obesity, and the mechanisms by which the gut microbiota influence energy metabolism and inflammation in obesity. Lastly, we focus on the potential role of LAB in mediating the effects of the gut microbiota in the development of obesity.     

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.     

Probiotics,antibiotics and the immune responses to vaccines

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome.     

Focus: Microbiome: Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation

The worldwide prevalence of metabolic syndrome, which includes obesity and its associated diseases, is rising rapidly. The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome. One way to modify the human gut microbiome is by transplanting fecal matter, which contains an abundance of live microorganisms, from a healthy individual to a diseased one in the hopes of alleviating illness. Here we review recent evidence suggesting efficacy of fecal microbiota transplant (FMT) in animal models and humans for the treatment of obesity and its associated metabolic disorders.     

A review on prebiotics and probiotics for the control of dysbiosis: present status and future perspectives

Dysbiosis or dysbacteriosis is defined as a shift in the intestinal microbiota composition resulting in an imbalance between beneficial and harmful bacteria. Since the ban on the use of growth-promoting antibiotics in animal feed in the EU, dysbiosis has emerged as a major problem in intensive animal production. Prebiotics and probiotics are currently under investigation as possible alternatives to growth-promoting antibiotics, as their mode of action is thought to be based largely on a modulation of the composition and function of the intestinal microbiota. In this review, we analyse the currently available data from both animal and human nutrition that document the potential and limitations of prebiotics and probiotics for the control of dysbiosis. An impressive number of empirical feeding trials have been carried out in healthy animals, yielding sometimes contradictory results. More in-depth studies have revealed the complexity of the interactions taking place in the lower intestinal tract, thus illustrating that pre- and probiotics cannot be a simple replacement for growth-promoting antibiotics. Although there are indications that the strategic use of pre- and probiotics can provide major benefits, there is still a lack of basic knowledge on the delicate interactions between the microbiota, the host and the feed components, which hampers the widespread use of these valuable feed additives.     

Hazard Group 3 agent decontamination using hydrogen peroxide vapour in a class III microbiological safety cabinet

Probiotics administration in aquafeed is known to increase feed consumption and absorption due to their capacity to release a wide range of digestive enzymes and nutrients which can participate in digestion process and feed utilization, along with the absorption of diet components led to an increase in host’s health and well-being. Furthermore, probiotics improve gut maturation, prevention of intestinal disorders, predigestion of antinutrient factors found in the feed ingredients, gut microbiota, disease resistance against pathogens and metabolism. The beneficial immune effects of probiotics are well established in finfish. However, in comparison, similar studies are less abundant in the shellfish. In this review, the discussions will mainly focus on studies reported the last 2 years. In recent studies, native probiotic bacteria were isolated and fed back to their hosts. Although beneficial effects were demonstrated, some studies showed adverse effects when treated with a high concentration. This adverse effect may be due to the imbalance of the gut microbiota caused by the replenished commensal probiotics. Probiotics revealed greatest effect on the shrimp digestive system particularly in the larval and early post-larval stages, and stimulate the production of endogenous enzymes in shrimp and contribute with improved the enzyme activities in the gut, as well as disease resistance.     

Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice

Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes, and even other immunological disorders.     

Nutrition Facts in Multiple Sclerosis

The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.