Paper intensive reading (三)：Interactions Between Food and Gut Microbiota: Impact on Human Health
论文题目：Interactions Between Food and Gut Microbiota: Impact on Human Health
Volume publication date March 2019
YanbeiWu, JiaweiWan,..., Thomas T.Y.Wang
Published in Annual Review of Food Science and Technology
Google citation: 2
Abstract
Understanding the relationship between food and the gut microbiota, their interactions, and how each modulates the other is critical for successful promotion of human health. This review seeks to summarize (a) the current knowledge on the effects of food and food components on gut microbiota and (b) the association between gut microbiota, consumption of food, and food bioactive components and the resulting beneficial health outcomes. Our goal is to provide state-of-the-art information on food and gut microbiota interactions and to stimulate discussions and research approaches that will move the field forward.
Keywords
gut microbiota, disease, human health, food, food components
Outline：
1. Introduction
2. What is the gut microbiota?
3. Factors that influence gut microbiota
4. Interactions between gut microbiota and human diseases
4.1 Obesity
4.2 Inflammatory Bowel Disease
4.3 Cancer
5. Impact of food on the gut microbiota and its relationship with human health
5.1 Plant-based food
5.2 Animal-based food
5.3 Fermented foods
5.4 Food Addictives
6. Future prospects
In summary, a complex interactive relationship between food and the gut microbiota exists and is receiving intense to provide information on how the interaction can produce either positive or negative effects on human health. The future holds exciting opportunities as well as challenges. In the current state of human health sciences, precision nutrition and individual medicine dominate our future direction on studies of human health. In this context, it will be critical to individualize gut microbiota and tailor individual foods that can modulate an individual's gut microbiota for health. The challenge will be to identify optimal combinations of the variables. This will open up the opportunity for food technologies to produce designer foods that help achieve optimal human health. Partnerships among plant geneticists, growers, food scientists, and nutritionists will be necessary to achieve the goal. A critical factor to be addressed is exposure time. In some cases, the biological efficacies may take years to manifest; therefore, population scientists may be integral to addressing this issue. Validation of biological efficacies, with or without alterations at individual levels, will be critical. Translational and basic scientists (e.g. omics scientists) as well as food scientists will need to collaborate to address this question. The ability to produce foods that are nutritions and tasty and at the same time tailored to benefit the human gut microbiota and health requires trans-disciplinary approaches conducted by many partners who understand how food modulates the gut microbiota to promote human helath.
根据个人肠道菌群进行个性化饮食，个性化用药推荐，但是生物学效应大部分在很长时间内才能看到效果。需要很多学者的合力。
1. Introduction
Recent advances in nutritional research support the importance of the human gut microbiota in the regulation of human health. 肠道菌群对调节人体健康的确非常重要。
There is no lack of information in the literature on the possible health-promoting effects of food or food bioactive components and their potential mechanisms of action. Efforts to understand the effects of food and food bioactive components on the human gut microbiota and the role of such interaction on the modulation of human health have just begun. 关于食品或食品中某些成分有利于人体健康的文献有很多，但是了解食品和食品生物活性成分对人体肠道菌群的影响以及这种相互影响对人类健康的作用方面的研究才刚刚起步。
The aims of this review are to summarize：本review内容分两个层面
(a) the current knowledge of the effects of food and food components on the gut microbiota 食物和食物成分对肠道菌群的作用
(b) the association of dietary components and gut microbiota with beneficial health outcomes. 饮食成分和肠道菌群与有益健康的关系
这两个层面在Role of the gut microbiota in nutrition and health中也有体现
Effect on gut microbiome 体现为肠道菌群的变化，这个菌减少了，那个菌增加了这种
Effect on health outcomes mediated by gut microbiome 体现为表型，这个疾病的症状减轻了? 就是一个对人体的影响了
Understanding the role of food and its bioactive components on influencing and modulating gut microbiota would provide
(a) critical information to further our knowledge on the potential mechanisms of action of food and food bioactive components on health and 了解食品和食品生物活性成分对健康的潜在作用机制
(b) sciencebased information to promote the use of food in the prevention of diseases and advancement of human health. 促进食品在预防疾病和提升人类健康水平方面的作用
2. What is the gut microbiota?
首先来了解一下什么是肠道菌群
Table1 The composition of human intestinal microbiota
| Phylum(门) | Relative abundance (%) | |
| Infant (<1-year-old) | Adult | |
| Firmicutes(厚壁菌门) | 32.01 | 50.5 |
| Bacteroidetes(拟杆菌门) | 20.08 | 48 |
| Proteobacteria(变形菌门) | 46.14 | 0.6 |
| Actinobacteria(放线菌门) | 1.28 | 0.2 |
| Verrucomicrobia(疣微菌门) | 0.44 | 0.6 |
| Fusobacteria(梭杆菌门) | 0.06 | 0.08 |
| Unclassified | NA | 0.02 |
The functions include defending the host against pathogens(保护宿主免受病原体侵害)、altering digestion and absorption of nutrients、producing essential nutrients such as vitamins (K and B)、and modulating our immune system and immune-related health issues. 肠道菌群主要的四大功能
Several taxa, including Prevotella(普氏菌属), Acinetobacter(不动杆菌属), Desulfovibrio(脱硫弧菌属), Veillonella(韦永氏球菌属), and Clostridium perfringens(产气荚膜梭菌), tend to exist transiently. 还有一些菌群是短暂存在的。
By 2.5 years of age, the gut microbiota becomes stable and is similar to that of an adult; however, it continues to evolve at a steadier and slower rate throughout the entire life of an individual. 在2岁半的时候，肠道菌群趋同于成年人。后续缓慢进化。所以才提倡母乳到2岁？因为母乳肯定更利于婴儿的肠道菌群健康进化吧？
The microbiota developmental period from birth to 2.5 years may be critical, and the disruption of the gut microbiota in early infancy may seriously impact human health (e.g., obesity, digestive system disease, and cancer) later in life. 所以真的不能乱喂，很多小时候总是喂太多，太胖，成年了也变成了易胖体质。很难减肥。
There are extremely diverse bacteria and other microbes colonized in the human intestine, including archaea, fungi, and, arguably, viruses. 肠道中也有古菌，真菌和病毒。
A rough estimate of 1,000 bacterial species in the gut with 2,000 genes per species yields an estimate of 2,000,000 genes, which is approximately 100 times more than the number of human genes. 肠道菌群的基因总数是人类基因总数的100倍。
In general, the gut microbiota is similar in healthy individuals, but species composition is personalized and largely determined by environment and dietary habit. 在健康个体中，肠道菌群总体类似，但是组成是个性化的，取决于环境和饮食习惯。
A healthy and balanced gut microbiotamay thus be a key to ensure human health.
3. Factors that influence gut microbiota
The first contact site is either the mother’s vagina or skin depending on the delivery system. 对于婴儿来说，分娩方式会影响婴儿的肠道菌群，一般来说，自然分娩的婴儿比剖腹产的婴儿肠道菌群多样性更高，更有利于健康。
Whether the infant is breast or formula fed also affects their gutmicrobiota. 喂养方式也会影响婴儿的肠道菌群。
Colostrum, known as the first milk, contains immune cells such as lymphocytes and many antibodies such as IgA, IgG, and IgM. 初乳非常重要~~~~淡黄色，而且小宝宝的胃一开始只有5ml那么大，完全够喂饱它了。
it was reported that the nutritional component in breast milk could promote the growth of Lactobacillus and increase total short chain fatty acids (SCFAs) in feces, suggesting a beneficial effect of breast milk on host intestinal health. 母乳对肠道健康有益
Over the past two decades, studies found that bifidobacteria were the most dominant species in both breast- and formula-fed infants. 过去二十年的研究表明，双歧杆菌是母乳喂养和配方奶喂养的婴儿肠道中的主要菌种。双歧杆菌属于放线菌属。有研究表明母乳喂养的婴儿肠道中的双歧杆菌细胞数目是配方奶喂养婴儿的两倍。
These changes are influenced by various factors, including, but not limited to, antibiotics, disease, injury, surgery, stress, and diet. 人的肠道菌群会一直发生变化，影响因子包含但不局限于抗生素、疾病、伤病、手术、压力和饮食。抗生素使用对肠道菌群的影响被普遍研究。
Colonization resistance is defined as a defense mechanism in which the intestinal microbiota protects the host against harmful microorganisms. 定殖抗性，抗生素治疗会影响肠道的定殖抗性。
antibiotic treatment can diminish bacterial diversity.
抗生素治疗恢复需要很长时间，对肠道菌群产生的影响能持续四年之久。
4. Interactions between gut microbiota and human diseases
The dysbiosis of the gut microbiota has been linked to an increased risk of various diseases, such as obesity, inflammatory bowel disease (IBD), cancer, diabetes, psychiatric disorders(精神疾病), and asthma(哮喘).
4.1 Obesity
It was found that genetically obese mice had higher Firmicutes to Bacteroidetes ratio compared to lean mice and that Firmicutes helped the obese mice to absorb more calories from the ingested diet, thus leading to obesity. 研究发现，与瘦老鼠相比，从基因上肥胖的老鼠拥有更高的厚壁菌门与拟杆菌门的比率，厚壁菌门有助于肥胖老鼠从摄入的食物中吸收更多的热量，从而导致肥胖。所以厚壁菌门是肥胖人群所谓喝水都胖的原因~
In addition, obese individuals have less microbial diversity than do lean individuals, and dietary intervention appeared to improve the microbial richness and associated clinical phenotypes, such as an improvement ofmetabolic and inflammatory status.
The role of microbial populations at the genus and species levels in obesity has also been investigated, but it is noteworthy that some results were not consistent, especially in the Lactobacillus(乳酸菌) species. 研究结果不一致，有一些研究表明在肥胖人群中乳酸菌的数目增加，而在一些肥胖小鼠的研究中发现，乳酸菌具有抗肥胖作用。这种相反的结果，那一定是忽略了一些其他的因素？数目增加，比例呢？会不会比如说乳酸菌跟另外一种菌相互作用才能抗肥胖？但是这种相互作用很复杂吧。
showed that higher levels of Bifidobacterium(双歧杆菌) animalis, Lactobacillus paracasei(副干酪乳杆菌), and Lactobacillus plantarum(植物乳杆菌) were associated with normal weight, whereas enrichment with Lactobacillus reuteri(罗伊氏乳杆菌) and depletion of Methanobrevibacter smithii(史密斯甲烷杆菌) were associated with obesity.
Similarly, there are inconsistencies in correlating Faecalibacterium prausnitzii(普氏杆菌) with obesity. 有研究表明肥胖儿童的普氏杆菌的比例比非肥胖儿童的高。然而，在糖尿病个体中发现了比较少的普氏杆菌，而且普氏杆菌的增加与轻微炎症的缓解相关。这种现象是不是存在一个阈值啊？比如说超过某个阈值就不好了，但是低于某个阈值是有利？属于拟杆菌门
Studies conducted so far suggest that the gut microbiota plays a key role in the etiology of obesity and offers an opportunity to prevent or treat obesity via its modulation.Nevertheless, the causal effects of specific microbial groups on obesity warrant further elucidation. 肠道菌群在肥胖学的病因中有重要作用，但是具体的影响机制还需要进一步的研究。
4.2 Inflammatory Bowel Disease
An imbalance of gut microbiota with alterations in the mutual relationships between the gut microbiota and the host may facilitate the formation of IBD.
In most of the studies, the changes in gut microbiota composition in IBD patients were correlated to the level of Firmicutes and Proteobacteria in the gut. IBD病人与肠道中厚壁菌门和变形菌门水平有关。
a study in 2006 reported that a reduction in the diversity of the gut microbiota was observed in IBD patients, and it was largely due to a decrease in the diversity of Firmicutes. 厚壁菌门较少，肠道炎症，这说明厚壁菌门跟炎症之间是什么关系呢？谁是因，谁是果？
Among Firmicutes, a decrease in the Clostridium leptum groups(梭状芽胞杆菌), especially F. prausnitzii(普劳氏菌), has been consistently reported as one of the main butyrate producers found in the intestine.
In contrast, changes in Enterobacteriaceae, Bacteroides, Bifidobacterium species, Lactobacillus species, and Escherichia coli are not consistent among studies. 相反，研究中肠杆菌科，拟杆菌属，双歧杆菌属，乳杆菌属和大肠杆菌的变化不一致。
Medication also may affect the composition of the gut microbiota.
Metabolites of the gut microbiota contribute to epithelial cell function, energy balance, and the immune system of the host. 肠道菌群的代谢物有助于肠道上皮细胞功能，维持能量平衡和宿主的免疫系统。
However, it remains unclear whether the dysbiosis observed in IBD is a cause or a consequence of intestinal inflammation.肠道菌群失调和IBD，谁是因，谁是果，目前并不清楚。
A long-term study in the microbiota’s changes in IBD patients may be necessary and warrants further study.
4.3 Cancer
The etiology, development, and progression of specific cancers are all different; hence, cancer is actually many different diseases. 癌症实际上是许多种不同的疾病。
Genetics and environmental factors (such as diet and exposure to environmental agents) are thought to be important modulators in the carcinogenesis process. 遗传和环境被认为是癌症最重要的影响因素。
Recent advances in sequencing technology and bioinformatics have highlighted the human gut microbiota as a critical regulator of human physiology. 人类肠道菌群被认为是人类生理调节的重要因子。
鉴于致癌原因和肠道菌群作用的复杂性，本review只讨论几种重要的癌症。
结肠癌是美国第三大癌症
Several studies reported significant differences in the abundance of specific bacteria in the gut microbiota of patients with colon cancer compared to that of healthy controls. 结肠癌病人与健康对照组病人特定集中菌的丰度差异。
reported significant differences between the mucosal microbiota composition of colorectal cancer patients and that of controls. 黏膜菌群组成的显著差异。
Fusobacterium nucleatum, in particular, has been extensively studied as a potential causal effector for colon cancer. Increased abundance of F. nucleatum has been found in the colorectal cancer metagenomes. 梭杆菌属在结肠癌中被广泛研究。
Fusobacterium is suggested to be a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development. 但是梭杆菌属被认为是癌症条件下的果，而非因。
The mechanisms by which gut microbiota modulate colon carcinogenesis remain unclear. 肠道菌群与致癌原因的作用机制尚不明确。
The potential mechanisms may include modulation of immune responses, xenobiotic metabolisms,DNA methylation, and DNA damage. 潜在机制。
In addition, several factors have been identified as gut microbiota–derived potential regulator/ effectors of colon carcinogenesis, and include the concentration of SCFAs, bacteria–bacteria toxins, and bacteria-generated metabolites. 其他几个被认为是致癌原因的因素。
乳腺癌是美国女性第二大死亡癌症，Breast cancer 女性雌激素
The enzymatic products generated by enteric bacteria are capable of metabolizing estrogens. 肠道细菌的酶产物能够代谢雌激素。
alterations to the microbiota may lead to breast cancer that is associated with the availability of estrogen recycled into circulation. In addition, chronic inflammation is known to be associated with the development of breast cancer. 雌激素，慢性炎症，研究肠道菌群和乳腺癌的切入点。
Obesity, a known risk factor for breast cancer carcinogenesis, causes gut microbiota dysbiosis, leading to chronic inflammatory state. 肥胖也是乳腺癌的高风险因子，so~~~
perturbation of gut microbiota and thus inflammation may link obesity to development of breast cancer.
5. Impact of food on the gut microbiota and its relationship with human health
Food choices play an integral part of a healthy lifestyle, and the gut microbiota act as a bridge between food and promotion/modulation of human health. 食物选择是健康生活方式必不可少的组成部分，而肠道菌群是食物和有益人体健康之间的桥梁。
The long-term diet, as well as a short-term macronutrient change, can rapidly and reversibly alter the genomic composition and metabolic activities of microbiota in the human gut. 长期饮食以及短期的大量营养素变化可以迅速和可逆地改变人类肠道菌群的基因组组成和代谢活性。
the changes in the gut microbiota are distinct in response to different types of food. 因此分四类食物进行讨论。
5.1 Plant-based food
西蓝花可以改善结肠炎状态，难怪都说西蓝花营养价值高。。。
然而，it is noteworthy that there is a big difference between the changes in themicrobiota of different animal models, even when they were fed the same food. 不同的动物吃同样的食物，微生物群的差异会很大。即便是同为人类，吃相同的食物，肠道微生物菌群也会有差异的，更别提不同的动物了。
cereal(谷类) foods are considered as a kind of prebiotic to be utilized by colonic bacteria that can improve host health. 难怪益生元干预实验很多都是用什么谷物？
但是，not all cereal foods have similar actions.
比如说，the effect of cereal products on intestinal microbiota composition varies depending on their type, especially the level of refinement, and intervention time.
Individual components of plant-based foods have also been examined formodulation of microbiota and health.
植物性饮食的主要成分是碳水化合物。
Digestible carbohydrates are broken down by enzymes in the small intestine and release glucose into the bloodstream,whereas nondigestible carbohydrates (resistant starch, dietary fiber, and oligosaccharides(低聚糖)) travel to the large intestine, where fermentation by microbes in the anaerobic(厌氧) environment of the gut can occur. 可消化的碳水化合物被小肠中的酶分解并释放葡萄糖到血流中，而不可消化的碳水化合物（抗性淀粉，膳食纤维和低聚糖）进入大肠，在肠道的厌氧环境中微生物会发生发酵 。
Bacteroides(拟杆菌属), Roseburia(罗斯氏菌属), Ruminococcus(瘤胃球菌属), and Bifidobacterium species are known to utilize undigested carbohydrates (resistant starch, xylan(木聚糖), cellulose(纤维素), and oligosaccharides(低聚糖)) to provide the host with energy and carbon sources.
a greater increase in SCFA production, particularly butyrate, may reduce the risk of developing GI disorders, cancer, and cardiovascular disease.
Many studies suggested that increased consumption of nondigestible carbohydrates could result in high taxonomic and microbial gene richness, which associated with a low risk of adiposity and dyslipidemia and a less pronounced inflammatory phenotype in contrast to individuals with low bacterial richness. 难怪都推荐多吃蔬菜，原因在于不可消化的碳水化合物，抗性淀粉、膳食纤维、低聚糖等。
Resistant starch in the grain may behave as a growth substrate for these probiotic bacteria. 谷物中的抗性淀粉可以提供益生菌的生长基质。
high-fiber feeding could result in stronger co-occurrence patterns between the genus-level taxa 多吃高纤维食物
In addition to nondigested carbohydrates, dietary polyphenols(多酚) are an important group of bioactive compounds commonly found in fruits and beverages such as tea and red wine. 多吃水果、适量饮茶、喝红酒
The colonic microbiota is responsible for metabolizing the original polyphenols into a series of smaller phenolic metabolites with different physiological significance. 结肠微生物将多酚代谢成一系列具有不同生理意义的更小的酚代谢物.
Interestingly, because of interindividual diversity in microbiota composition, only approximately 30%–50% of Western women are able to produce equol(雌马酚). 大豆中的类黄酮
The effect of dietary polyphenols on gutmicrobiota and human health has been studied in vivo and in vitro. Polyphenol-rich foods such as grapeseed, wine, cocoa, and green tea extracts often show prebiotic-like effects on gut microbiota that induce the growth of lactobacilli and bifidobacteria. 养生指南。。。葡萄籽油、红酒、可可粉、绿茶
polyphenols may regulate microbiota to protect obesity and obesity-related risk factors.
plant-based foods appear to increase the number and activities of beneficial microbiota in the gut, which correlates with promotion of health.
5.2 Animal-based food
The gut microbiota composition can be rapidly shifted by animal-based foods such as meats, eggs, and cheese.
The levels of Firmicutes(厚壁菌门) that metabolize dietary plant polysaccharides (Roseburia(罗斯氏菌属), Eubacterium rectale(直肠真杆菌), and Ruminococcus bromii(布氏瘤胃球菌)) were found to be lower in human populations whose diet is rich in animal protein and fat.
Prevotella, the one genus positively correlated with a vegetable-rich diet, was reduced in vegetarians after consumption of the animal-based diet. 普氏菌属，随着动物性饮食增加而减少
Animal-based foods provide protein, fat, and other key essentialmicronutrients (e.g., iron, zinc, vitamin A, vitamin B12) to humans. 所以全素食也不行吧
Significant increases in bile acids as well as their metabolic products in feces may have contributed to the microbial disturbances and have implications for colonic cancer risk.
animal-sourced saturated and unsaturated fats have profoundly different effects on the gut microbiota 动物性饱和脂肪和不饱和脂肪对肠道菌群的影响是截然不同的
A. muciniphila is a mucindegrading bacterium that abundantly colonizes nutrient-rich environments. The number of A. muciniphila was reduced in obese and type 2 diabeticmice. A. muciniphila在营养丰富的肠道中繁殖，在肥胖和2型糖尿病小鼠中减少，这是说肠道菌群的减少是疾病的结果。
Consumption of a prebiotic (oligofructose) could normalize A. muciniphila abundance, abolish metabolic endotoxemia, and suppress expression of macrophage infiltration maker in adipose tissue of mice. 摄入益生菌可以使A. muciniphila的丰度增加，从而消除代谢内毒素血症，抑制巨噬细胞浸润因子在小鼠脂肪组织中的表达。
fish oil might protect against diet-induced obesity via upregulating the intestinal probiotic abundance that correlates with an improved metabolic profile.
Tryptophan(色氨酸) is an essential amino acid that must be obtained from food such as red meat, fish, and eggs. 色氨酸必须从红肉、鱼、蛋中摄取。
In summary, the relationship between animal-based food microbiota and health seems to be complicated. 牵涉到人体，关系有不复杂的吗。。。
Unlike plant-based foods, animal-based foods do not have consistent patterns of healthy versus nonhealthy effects. 与植物性饮食有区别
It would be difficult to ascribe generalized healthy or unhealthy food based on their regulation of the gut microbiota. 很难说一个动物性食物是健康还是非健康
5.3 Fermented foods
An increasing number of studies have documented that fermented foods exhibit enhanced nutritional and functional properties because of the transformation of substrates and formation of bioactive metabolic products by microorganisms. 发酵食品有益健康
Most fermented foods also contain living microorganisms, some of which may contribute as probiotics to the promotion of human health.
In a subset of the patients, IBS symptoms were alleviated by the probiotic treatment (Matijaši´c et al. 2016). 可收集数据集哦
经常食用酸奶，能抑制一个苯酚，防止皮肤老化。。。
In addition to fermented milk and because of the benefits of the fermentation process, some new types of food material have been fermented. 如发酵绿茶，发酵蓝莓，
Fermented foods provide multiple elements, including probiotics, prebiotics, and novel bioactives, that may alter the gut microbiota and human health. 但是发酵食品对肠道菌群的改善大部分都是短暂的，所以最好就持续摄入喽~
the probiotic bacteria in fermented foods may be affected by diet and other gut-associated factors; thus, further studies are warranted to investigate the long-lasting effects of fermented food on resident gut microbiota and human health. 进一步研究
5.4 Food Addictives
Food additives can be divided into several groups, including flavors, colorants, emulsifiers, sweeteners, and thickeners. 食品添加剂可以分为几种，包括香料、着色剂、乳化剂、甜味剂和增稠剂。
Emulsifiers and artificial sweeteners have been reported to promote the development of metabolic syndrome by perturbing the host-gut microbiota relationship.
The increase of flagellin, a bacteria-derived protein, was sufficient to induce low-grade inflammation and metabolic syndrome. 鞭毛蛋白，可引起轻微炎症和代谢综合症
consumption of noncaloric artificial sweeteners that induce the compositional and functional alteration of gutmicrobiotamight enhance the risk of glucose intolerance in bothmice and humans. 无热量甜味剂会增加小鼠和人类葡萄糖不耐受的风险
accumulating data suggest that artificial food additives might contribute tometabolic disease throughmodulation of themicrobiota.
However, the related studies are limited, making it necessary to conduct additional studies to include the relationships between food additives, gut microbiota, and human health. 食品添加剂、肠道菌群和人类健康的关系需要进一步研究。
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