Impact of gut microbiota on neurological diseases: Diet composition and novel treatments

ABSTRACT

Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.     

益生菌对结直肠癌的改善作用与机制的研究进展

结直肠癌（Colorectal cancer , CRC）是全球最常见的癌症类型之一,也是全球第二大癌症相关死亡原因。近年来,我国结直肠癌发病率已跃居第二位,对其防治也越来越重视。研究发现肠道菌群结构与CRC的发生发展密切相关。益生菌作为肠道有益微生物,具有调节肠道免疫、增强肠道屏障和维持肠道菌群结构平衡等功能,在CRC预防和辅助治疗方面扮演重要角色。本文综述了肠道菌群对CRC影响以及益生菌对结直肠癌作用机制的研究进展,以期为益生菌预防和缓解CRC提供理论基础。     

益生素、益生菌与结肠癌

介绍了益生素和益生菌及其作用机理。在动物模型中，有大量的数据证实益生素和益生菌能够预防癌症．而在人体内还没有直接实验证据。它们抑制癌症的确切机理目前尚不清楚，其抑制机理可能是：肠道菌群代谢活动的改变，肠道理化环境的改变，潜在的致癌物质的黏附和降解，肠道菌群的改变、抗癌或抗诱变物质的形成、提高宿主的免疫应答、影响宿主的生理活动以及发酵不能被消化的食物并形成有益代谢产物。     

Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention

Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.     

The Beneficial Use of Cereal and Cereal Components in Probiotic Foods

Cereals and cereal components can be used as fermentation substrates for probiotic organisms imparting prebiotic effects. Consumer interest in healthy functional foods has resulted in the need for food products with versatile health-benefiting properties. The conventional choice for probiotic food applications has been dairy-based products, but whole grain-based probiotic functional foods have debuted in Japan and Europe. In the US, pro- and prebiotics are mainly marketed as dietary supplements, but are moving towards inclusion in the diet as mainstream foods. Cereal constituents, such as wheat bran-based ingredients fermented with probiotics, would enhance consumer health with the benefits of probiotics, bran fiber, and healthful bioactive components.     

Effect of different complex carbon sources on growth and bacteriocin synthesis of Enterococcus faecium

Different criteria are followed in order to select bacteria to be used in probiotic and symbiotic supplements. A new parameter to choose strains could be fermentation by intestinal bacteria of some complex carbohydrates because they are prebiotics and promote the development of beneficial microorganisms in the intestinal environment. An Enterococcus faecium strain, isolated from the crop of a free-range chicken, was assayed in order to determine the utilization of commercial sugars and/or crude carbohydrate samples from a sugar mill. The production of antimicrobial substances, under these conditions, was also considered. Ent. faecium CRL1385 grew well in the presence of complex carbohydrates and its ability to produce bacteriocin, active against poultry pathogens such as Ent. hirae, Salmonella pullorum and Listeria monocytogenes, was not significantly modified. These results are promising because the trend today is to employ eubiotic or symbiotic products and their use in the poultry industry could be a natural way to protect the flocks against potential pathogens.     

国外益生元膳食来源与摄入量现状

介绍了益生元的概念及其特征,根据不同国家的地区现状对益生元的膳食来源和摄入量进行了探讨,为满足人们对益生元的健康需求结合天然食品、营养强化食品以及营养补充剂给出了膳食建议,讨论了影响国外消费者选择益生元食品的原因。     

Non-digestible oligosaccharides with prebiotic properties

The search for functional foods or functional food ingredients, i.e. foods or food ingredients that can enhance health, is beyond any doubt one of the leading trends in today's food industry. In this context, probiotics, i.e. living microbial food supplements, and prebiotics, i.e. non-digestible food ingredients, receive much attention. Both popular concepts target the gastrointestinal microbiota. While in the Western world, intake of probiotics has been recommended for long, prebiotics in general, and non-digestible oligosaccharides in particular, have only recently received attention. This review deals with production and characterization of non-digestible oligosaccharides and focuses on their role in promoting health and treating diseases. Attention is paid to the effects of non-digestible oligosaccharides on constipation, mineral absorption, lipid metabolism, cancer prevention, hepatic encephalopathy, glycemia/insulinemia, and immunomodulation.     

Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils

In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9?±?8?ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3?ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.     

Influence of functional food components on gut health

Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.     

Food properties and dietary habits in colorectal cancer prevention and development

Colorectal cancer (CRC) is a very common and lethal disease worldwide. The etiology of the disease includes genetic and environmental factors. Among environmental factors, the dietary habits are considered to be easily changeable regarding preventing the CRC. Although there is still a long road to cover the gaps in knowledge on nutritional determinants and the dietary pattern on the CRC risk, several dietary suggestions and goals could be summarized. Diets high in energy, consumption of red meat or processed meat, food with a high glycemic index (carbohydrates, snack food, frying fast food, and sugar-sweetened drinks, sweets), exceed intake of salt (NaCl), low daily water intake (<4 cups per day) have been linked to an increased CRC risk. In contrast, consumption of white meat, as well as plant and fish oils with a high omega-3 PUFA to omega-6 PUFA ratio might even reduce the occurrence of CRC. A fiber-rich diet can lower the CRC risk up to 50%. Diet rich in vitamin B6, C, D, E, folic acid, selenium, and magnesium has also been considered to reduce the CRC risk. General unhealthy lifestyle which results in overweight and obesity-related syndromes (chronic inflammation, type 2 diabetes) can promote CRC. However, in many cases, the results are inconsistent and depend on multiple interdependent factors, i.e., ethnic, anthropometric, gender, age, hormones, and environment. In addition to dietary habits, all these agents are suggested to modify the risk of CRC.     

Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association

Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.     

生命早期肠道菌群的建立和变化及对婴儿健康的影响

人类肠道中聚集着丰富的微生物群落,肠道微生物甚至在婴儿出生前就已经开始定植.从妊娠期开始到婴儿2岁都是肠道菌群发育的机会窗口.在此期间,肠道菌群的组成容易受到孕龄、分娩方式、喂养方式、抗生素、益生菌和益生元、环境因素和宿主基因等多种因素影响.肠道菌群对婴儿日后的发育至关重要,与婴儿健康密切相关.该综述讨论了生命早期肠道...     

低聚半乳糖的生理功能研究进展

低聚半乳糖作为一种益生元越来越受到人们的关注,在功能性食品方面应用越加广泛。低聚半乳糖能够在肠道内选择性增殖益生菌发酵生成短链脂肪酸,与肠道微生物协同参与生理功能机制调节,在保障肠道健康、免疫系统调节、抑制肿瘤细胞生成、改善人体矿物质吸收、改善心血管疾病等机制方面发挥重要的作用。本文从分子水平出发,全面剖析了低聚半乳糖及其代谢产物短链脂肪酸在维持肠道微生物平衡、抵抗肠道病毒感染、免疫机制调节、结直肠癌的抑制、脂质代谢的调节及血糖水平控制等功效方面的作用机理。为低聚半乳糖在功能性食品开发及健康保健领域的应用提供参考。     

5种益生元润肠通便功能的比较研究

为了比较不同益生元润肠通便的功能差异,将168只昆明雄性小鼠,随机分为两组,一组进行小肠运动实验,一组进行排便实验,两个实验分别设有空白对照组、模型对照组、水苏糖组、低聚果糖组、低聚半乳糖组、聚葡萄糖组、菊粉组,5种益生元的干预剂量均为1.0 g/kg,干预14 d后,利用盐酸洛哌丁胺建立小鼠便秘模型,测定小肠墨汁推进率、首例排黑便时间、6 h内排黑便例数和粪便重量。小肠运动实验结果表明,与模型对照组相比,水苏糖、低聚果糖、低聚半乳糖、菊粉组的小肠墨汁推进率均明显增加,差异具有统计学意义(P<0.05);聚葡萄糖组小肠推进率有增加趋势,但差异不显著。排便实验结果表明,5种益生元的首例排黑便时间、6 h内排黑便粒数和粪便重量均无明显差异(P>0.05)。综上,在干预剂量为1.0 g/kg时,水苏糖、低聚果糖、低聚半乳糖、菊粉均对小肠运动具有促进作用,但对排便无影响;不同益生元对小肠运动的影响无显著差异。     

Prebiotics: Present and future in food science and technology

Because of its resident microbiota, the human colon is one of the body’s most metabolically active organs. The use of diet to fortify certain gut flora components is a popular current aspect of functional food sciences and prebiotics have a significant role. Prebiotics are selectively fermented ingredients that allow specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host well-being and health. Improved techniques for analysis of the gut microflora, new food manufacturing biotechnologies, and increased understanding of the metabolism of prebiotic inulin and oligosaccharides by probiotics are facilitating development. Such developments are leading us to the time when we will be able to rationally develop prebiotics for specific functional properties and health outcomes. Thus, this review will focus on the progress of prebiotics in food science and technology in understanding the important role of prebiotics in health, beginning at the rationale of gut microflora and interactions with prebiotics. Furthermore, the classification criteria, food applications and safety assessment of prebiotics as food ingredient is also discussed.     

The potential of sphingomyelin as a chemopreventive agent in AOM-induced colon cancer model: wild-type and p53+/- mice

A protective effect of sphingolipids on colorectal cancer (CRC) has been reported in certain mouse strains. It is unknown if sphingolipids are protective in a p53 deficiency mouse model of CRC. This study investigated the effect of sphingomyelin (SM) on intestinal sphingomyelinase (SMase) activity, colonic epithelial biology and azoxymethane (AOM)-induced CRC. Groups of wild-type (C57BL/6J) and p53+/- mice were fed 0.1% SM diet for 4 wk, administered a single AOM injection and then killed 6 h later to measure apoptosis and proliferation. Separately, both mouse types were fed 0.05% SM diet, administered three AOM injections and killed 33-38 wk later to measure tumour formation. SM significantly increased SMase activity and reduced proliferation (p < 0.05) in wild-type and p53+/- mice. SM did not regulate baseline apoptosis, apoptotic response to AOM or apoptosis in tumours, nor did it restore defective apoptosis in p53+/- mice. There was a nonsignificant trend to reduced tumour incidence with SM in wild-type (p = 0.15) and p53+/- (p = 0.12) mice. In conclusion, while increasing intestinal SMase activity and suppressing proliferation, SM did not promote any form of apoptosis and failed to achieve significant protection in these mice. Further investigation to understand the variable effect of SM in preventing CRC is warranted.     

Food and Dietary Supplement Package Labeling—Guidance from FDA's Warning Letters and Title 21 of the Code of Federal Regulations

Package labels for foods and dietary supplements must conform with Title 21 of the Code of Federal Regulations. This review provides guidance for the content and format of labels, including for the Nutrient Facts panel and Supplement Facts panel, and for drafting structure/function claims, health claims, and nutrient content claims. Also provided is guidance on how to refrain from drafting disease claims. Inappropriate disease claims on a food or dietary supplement compels FDA to review the product as a drug. Disease claims is the most common source of complaint in FDA's warning letters. This review makes use of all of FDA's warning letters that were published over a 14‐y span (2002to 2015). This is the first comprehensive review on package labels to make use of FDA's warning letters as a source document.