The influence of dietary factors on intestinal flora.

The relationship between intestinal flora and human hosts is influenced by dietary factors, which is an important part of maintaining the symbiotic relationship between intestinal flora and hosts. Dietary components contain substrates required for intestinal flora metabolism and affect the structure and function of human intestinal flora through a variety of ways. In this paper, the influence of diet on intestinal flora structure and metabolic function, as well as the role of dietary intervention in digestive diseases and other research progress are briefly reviewed.

1. Establishment of diet and intestinal flora

The environment in which the fetus grows and develops in the mother’s womb is considered sterile. Immediately after delivery, the intestinal flora of the newborn is established, and the bacteria can be found in the first meconium. The colonization of intestinal flora of newborn infants is affected by delivery mode. The colonization of intestinal flora of natural delivery infants is mainly colonized by bacteria genera from the mother’s vagina, such as Lactobacillus and Prevotella. However, the intestinal flora of infants delivered by cesarean section mainly came from the intestinal colonization of skin microflora. Infants and young children are affected by various factors during their growth and development, such as food intake, feeding mode, direct contact with the external environment, infection, antibiotic application, etc., and the diversity of their intestinal flora shows a rapid but disordered trend of increase. The intestinal microbiota of infants under 1 year old coexist with individual differences and similarities, which are mainly affected by infant feeding patterns. When the infant is weaned, more significant changes can occur, presenting a more stable, adult-like bacterial community structure. Drastic changes in the structure of infants’ intestinal flora mainly occur when they start to consume solid food. The diversity and stability of infants’ intestinal flora structure around 3 years old are similar to those of adults.

Breastfeeding plays an important role in the plasticity of intestinal microflora in infants and young children. Breast milk meets the nutritional and physiological needs of infants and young children (such as digestion and absorption of nutrients, immune protection and protection against potentially pathogenic microorganisms) that are bioactive and not available in formula milk. Breast-fed infants had the advantages of internal oxygen bacteria, and the colonization of Clostridium difficile and other Clostridium difficile were reduced, and the content of Bacteroides was low, while formula feeding infants mostly had anaerobe and facultative anaerobe. In addition, lactooligosaccharides are one of the main components of breast milk, which can maintain structural integrity when passing through the human digestive tract, and can provide nutrition for bifidobacterium and other bacterial species and promote their growth and reproduction after entering the colon. Studies have shown that the proportion of bifidobacteria in the intestines of breast-fed infants is significantly higher than that of formula-fed infants. Bifidobacterium has many beneficial functions, such as strengthening intestinal mucosal barrier function by activating pathogen defense and regulating intestinal immune system. Bifidobacterium has specific enzymes that can metabolize lactooligosaccharides and isosaccharides. For example, Bifidobacterium longum infantile can participate in carbohydrate metabolism. In recent years, it has been reported that the use of formula milk rich in oligosaccharides can increase the number of bifidobacteria in the intestinal tract of infants. In conclusion, the study of infant dietary intervention and the structure and function of intestinal flora is still worthy of further study.

2. Possible mechanism of dietary influence on intestinal flora

First, the diet modulates the symbiosis of native bacteria in the gut. Metabolic substrates of intestinal flora mainly come from the diet, such as components and prebiotics that can be used for microbial fermentation. Dietary regulation of intestinal transport time, for example, dietary fiber intake can increase colon transport rate, increase organic acid production, and then reduce intestinal pH, while methanogenic archaea can reduce intestinal transport time, which provides clues for the study of intestinal flora and functional gastrointestinal diseases. Food regulation of intestinal pH, such as dietary fiber intake can increase organic acid production and then reduce intestinal pH, intestinal pH is an important factor affecting the structure of intestinal flora. The main components of dietary protein and fat can stimulate mucins secreted by goblet cells of digestive tract, digestive enzymes secreted by pancreas and other tissues, and bile secretion, thus indirectly affecting the structure and function of intestinal flora. Bile acids also have antimicrobial effects and can also have an impact on intestinal flora. Diet can affect the expression of host and intestinal flora genomes, such as regulating the expression of genes related to carbohydrate metabolism in Bacteroidetes. Studies have shown that after long-term consumption of Marine algae products, enzymes encoding the metabolism of Marine red algae in Marine related bacteria can be transferred to specific microorganisms in the intestinal tract. In addition, food containing probiotics and fermented food in the diet can supplement the external microorganisms to the intestinal microecological environment and play an important physiological role. However, it should be noted that healthy adults have stable intestinal flora structure and high colonization resistance, and the extent of the probiotic effect of exogenous probiotics is still to be determined.

3.Dietary principal components and intestinal flora metabolism

In addition to regulating the structure and/or abundance of intestinal flora, diet can also be used as a substrate to participate in the metabolism of intestinal flora. After entering the intestinal tract, dietary principal components such as carbohydrates, protein and fat are mainly digested and absorbed in the small intestine, while undigested carbohydrates such as resistant starch, non-starch polysaccharides (NSP) and oligosaccharides entering the colon, as well as undigested proteins, begin to be metabolized by the intestinal flora. The metabolic process mainly includes three levels: degradation, fermentation and hydrogen treatment. In terms of dietary metabolic activity, many intestinal bacterial species had some functional overlaps. For example, Bacteroides, Prevotella and Ruminococcus were the main bacteria genus involved in the degradation, while Trichoderma, Ruminococcus, Bacteroides and Bifidobacterium were the main bacteria genus involved in the fermentation.

1. Carbohydrate: Carbohydrates such as resistant starch, NSP and oligosaccharides can avoid the digestion of host enzymes and reach the colon, where they are further metabolized by intestinal flora and can produce short-chain fatty acids (SCFA), hydrogen (H2), carbon dioxide (C02), methane (CH4) and other metabolisms. SCFA can provide energy to the host, regulate intestinal immunity and hormone release, and inhibit tumor cell proliferation. It mainly includes acetic acid, propionic acid and butyric acid, with a normal ratio of about 3:1:1. Butyrate is mainly absorbed and utilized by intestinal epithelial cells, and is the main energy source of the intestinal tract. It has the functions of regulating intestinal epithelial growth and development, maintaining intestinal barrier function, anti-tumor and anti-inflammatory activities, etc., which also suggests that intestinal butyrate producing bacteria can be used as beneficial strains for further study. Propionate is transported to the liver and is one of the main substrates for gluconeogenesis, while acetate is mostly absorbed and transported to the liver or to muscle and surrounding tissues, where it is mainly involved in lipid synthesis. Many bacterial species can produce H2 in the process of degradation and fermentation, and three low-abundance bacterial species, acetic acid bacteria, methanogens and sulfate reducing bacteria, are mainly involved in the processing of H2 in the colon. Many anaerobic bacteria can produce or utilize H2 through the action of reversible hydrogenase.

When the content of resistant starch, NSP and other carbohydrates which cannot be digested by the host is high, the beneficial fermentation process of intestinal flora can be increased, which helps to maintain intestinal health. Changes in carbohydrate intake and type can significantly and rapidly affect the structure of the intestinal microbiota and its metabolites in healthy individuals. Human Dietary Composition Intervention Studies have shown that consuming a diet rich in resistant starch or polysaccharides can significantly increase the amount of specific bacteria such as ruminococcus brucellii in the gut. In vitro studies based on human fecal samples have confirmed that these bacterial species selectively metabolize specific, nonsoluble carbohydrate substrates. Studies have found that African children than Europe high, intestinal flora richness in watford in intestinal flora species and bacteroides differences between the two species proportion, which may have originated from African farming diet (plants rich in carbohydrates and protein, etc.) with the European diet (high in animal protein and fat, etc.) related to different. Studies human intestinal flora structure can be divided into to in walter bacterium, bacteroides or rumen bacteria belong to three types, and found that rural populations in the gut to general walter species is given priority to, in the crowd and developed areas in the gut is given priority to with bacteroides, this may be related to different regional population dietary carbohydrates such as content in the high and low.

Human beings cannot encode enzymes that degrade plant-derived structural polysaccharides, and they need to rely on intestinal flora to degrade these plant cell wall components. For example, Ruminococcus brucinii plays a major role in the fermentation and metabolism of resistant starch, while Ruminococcus champanellensis is the main species and genus that decompose cellulose. Currently, there are four types of resistant starches (resistant starches 1 to 4), which are not degraded in the small intestine, reach the colon and fermentate under the action of intestinal flora to produce SCFA, improving the intestinal environment. Different species of starch-breaking bacteria in human intestines also have different metabolic abilities to various types of starch, such as ruminococcus brucinii and bifidobacterium youth, which have better metabolic activities to resistant starch 2 and 3. In addition, the low poly fructose and galactose and so on functional oligosaccharide is a typical prebiotics, cannot be absorbed by enzymatic hydrolysis in the small intestine, reached after the colon can produce SCFA, reduce intestinal pH value, promote the bifidobacterium and lactobacillus bacteria proliferation and inhibition of intestinal bacillus, salmonella and other harmful bacteria in the intestines of planting and breeding function.

2. Dietary protein: the residual dietary protein after digestion in the small intestine can provide nitrogen source for glycolysis bacteria and amino acids after fermentation and other metabolic processes by colonic flora. Bacteria such as Bacillus, Clostridium perfringens, Propionobacteria, Streptococcus, Bacillus and Staphylococcus, which contain serine and proteolytic enzyme genes, are mainly involved in protein decomposition in the intestinal tract. Metabolism of dietary protein by intestinal flora mainly occurs in the distal part of the colon, where pH value in the intestine is suitable and Bacteroides and other species have strong peptidase activity. In addition to producing SCFA and gas, dietary protein can also produce branching fatty acids, ammonia, phenols and/or indoles, N-nitroso compounds, amines and sulfides, most of which are harmful to the host intestinal tract. Long-term exposure of intestinal epithelial cells to protein-derived toxic metabolites may increase the risk of colorectal cancer and other intestinal diseases such as IBD. However, no direct evidence has yet been found to confirm the relationship between protein intake and intestinal diseases such as colorectal cancer and IBD.

Gastrococcus, Aminococcus, Veronococcus and Eubacteria have strong amino acid fermentation, but the ability of carbohydrate decomposition is low. The main pathway of amino acid fermentation in the intestine is deamination, which produces SCFA, branched chain fatty acids and ammonia base, etc., among which the fecal branched chain fatty acids content is often used as a marker of colon protein fermentation. The ammonia base in human feces increases with the increase of dietary protein intake, most of which is rapidly absorbed, metabolized by liver and excreted by urine, and has the role of stimulating intestinal tumor formation. Fusiform, bacteroidetes, enterobacteria, bifidobacteria and lactic acid bacteria can produce phenolic and indole substances by deamination of aromatic amino acids. LEIT substances are similarly absorbed rapidly through the colon and excreted in the urine after metabolism in the liver. Clostridium, Bifidobacterium and Bacteroidetes are related to the production of amines. A large number of amines can be produced by decarboxylation of amino acids and peptides, which are closely related to the metabolism of nitrosamines. Nitrosamines are known to be important carcinogens and can be detected in human faeces. Nitrosamine-producing bacteria were mainly aerobic bacteria such as Escherichia coli, Pseudomonas, Proteus and Klebsiella, and their content in colon was low. Hydrogen sulfide (H2S) is produced primarily by the metabolism of dietary sulfate by sulfate reducing bacteria. Elevated levels of sulfides in the colon may increase the risk of IBD.

At present, there are still few studies on the effects of dietary protein (meat, fish and plant protein) on the structure of intestinal flora, and mainly focus on the detection of protein fermentation products. For example, increased intake of red meat can significantly increase the content of sulfur compounds and N-nitroso compounds in feces. The content of fermentation products can be affected by changing the proportion of dietary protein and carbohydrate, but the effect on the structure of intestinal flora still needs to be further clarified.

3. Dietary fat: the degradation and absorption of dietary fat by various enzymes in healthy individuals mainly occur in the small intestine and rarely in the colon. Studies have shown that about 7% of fatty acids labeled by 13C can be excreted through feces. High fat diet can significantly reduce the diversity of intestinal flora and the total amount of bacteria, and significantly reduce the content of butyric acid and the number of bifidobacteria in feces. The content of some species of intestinal Bacteroides is related to the intake of polyunsaturated fatty acids and saturated fatty acids. A high fat diet significantly reduced the number of intestinal rosomycetes, which was restored with the addition of prebiotics, and the number of rosomycetes was negatively correlated with increased body mass, hypercholesterolemia, and genes involved in fatty acid uptake. High-fat diet can induce low-grade intestinal inflammatory response, which induces lipid-polysaccharides and other bacterial structural components from the intestinal tract into the circulatory system and leads to in vivo dissemination, which is manifested by the increase of plasma inflammatory response related indexes and endotoxin levels. The addition of prebiotics or xylans to a carbohydrate-free high-fat diet improved insulin resistance and reduced levels of pro-inflammatory factors.

Bile acid is one of the important factors affecting the composition of dietary flora, and plays an important role in the digestion and absorption of lipids, as well as the removal and excretion of many wastes produced by the body. The dysregulation of bacterial flora caused by high fat diet may be related to the promotion of bile acid secretion. The increase of dietary fat components and the lack of dietary fiber can increase the abundance of bile salt-tolerant bacteria such as choleophilus and bacteroidetes in the intestine, while the level of bacteria and genera involved in plant polysaccharide metabolism such as Rosomycetes, Eubacter rectum and Ruminococcus brucellii in the Firmicutes is decreased. High-fat diet promotes bile secretion, and bile acids enter the colon and interact with the intestinal flora encoding bile hydrolytic enzymes. For example, milk fat digestion and absorption can change the composition of bile acids in IL-10 knockout mice, promote the growth of cholilophilus, and further exacerbate the inflammatory response of the colon. Cholophilus may directly aggravate colonic inflammatory response, promote helper T cell-mediated immune response, and produce H2S and other small molecule toxic substances that can disrupt intestinal epithelial barrier function.

In general, there are few studies on the intervention of fat intake in humans at this stage. However, studies based on animal models strongly support the interaction between dietary fat and intestinal flora, but the existing studies are not in-depth enough.

4. Other dietary components and intestinal flora: Chinese medicine and food homologous ingredients also play an important role in regulating intestinal flora. The active ingredient of Chinese medicine Coptis is berberine, namely berberine, which has been used to treat bacterial diarrhea for a long time. Studies have shown that berberine can reduce blood glucose and lipid levels, inhibit the intestinal flora related endotoxin into the blood, and inhibit the inflammatory response level of the body, and prevent insulin resistance and obesity. In addition, the microbial metabolism of plant cell wall can promote the release of some phytochemicals with potential anti-inflammatory and antioxidant activities, such as phenols and flavonoids in foodborne phytochemicals. However, the bacterial species involved in this process have not been identified, which can be further explored as potential beneficial bacteria.

4. Dietary intervention and digestive diseases

Epidemiological investigation has confirmed that western diet is closely related to the incidence of IBD. For example, the more red meat patients with UC consume, the higher the risk of disease recurrence. A diet high in total fat, polyunsaturated fatty acids, omega-6 fatty acids, and meat is associated with an increased risk of IBD, while an increased intake of high-fiber vegetables and fruits is associated with a decreased risk. Diet can change the host’s immune response by affecting intestinal flora metabolism. For example, SCFA can activate G-protein-coupled receptors and regulatory T cells to strengthen the immune tolerance of intestinal mucosa. Enhance the fermentation capacity of intestinal flora and increase the production of SCFA can be used as one of the treatment strategies for IBD. Food antigens stimulate the gastrointestinal mucosal immune system, so total parenteral nutrition may be beneficial for some patients with IBD. Although total parenteral nutrition can achieve initial symptom relief in some patients with CD, relapse is more common; Existing evidence suggests that total parenteral nutrition can only improve symptoms in patients with severely advanced CD in the short term. In addition, total enteral nutrition is also an effective treatment for IBD. Studies have shown that total enteral nutrition can help induce and maintain remission in patients with CD, and some countries are considering it as a first-line treatment. Nutritional therapy can improve the structure of intestinal flora in patients with CD and has shown good efficacy in patients with CD. However, further studies are needed on the effect of total enteral nutrition on intestinal flora, as well as the specific mechanism and efficacy of using diet to treat and/or maintain remission of IBD. Low-fermentable oligosaccharides, disaccharides, monosaccharides, polyols and other artificial sweeteners with short chain carbohydrates are rapidly fermented by microorganisms in the colon to produce a large amount of H2, and are currently becoming a new therapeutic strategy for the treatment of gastrointestinal flatulence symptoms in patients with functional gastrointestinal diseases such as IBS.

5. Future research directions and prospects

Functional studies based on animal models, as well as descriptive and correlation studies based on human body, have provided a preliminary understanding of the interaction between diet and intestinal flora. Diet is one of the important factors affecting the structure and metabolic function of intestinal flora. The age and social dependence of intestinal flora are affected by different dietary habits and dietary structure. The influence of diet on intestinal flora starts from birth. For example, breast milk and formula feeding play a leading role in the early stage of human life and are important factors influencing the establishment of intestinal flora in the later stage. Long-term stable dietary structure is conducive to the maintenance of intestinal flora structure, while short-term dietary intervention can cause rapid changes in intestinal flora structure. Different dietary patterns (vegetarian and western diet, etc.) mainly affect the composition of intestinal flora in adults. The interaction between diet and intestinal flora has a profound influence on many physiological functions of human body. Dietary and intestinal flora play an important role in the occurrence and development of many digestive diseases such as IBD, IBS and colorectal tumors.

Although diet is an easy factor to control or change, studies on human diet intervention still face many difficulties: the complexity and heterogeneity of dietary components, scientific and rational intake, etc., are still to be clarified; The ethical issues and maneuverability of selectively adding or removing major dietary components in human studies; Even though the same fermentation substrate is used in the data of bacterial species, the end products of metabolism are complex and varied. In addition to diet and intestinal flora, host factors are also involved in the physiological function of diet. In addition to regulating the intestinal bacterial community, diet also affects the structure and function of the archaea and fungi community in the human intestinal tract, but the current research has not been in-depth. The study of gastrointestinal microecology requires a combination of omics methods such as nutriomics, metagenomics, macrotranscriptomics and metabonomics to stratify the population according to the characteristics of intestinal flora and host factors, which can help to reduce the heterogeneity of intestinal flora and its response to diet. Reasonable design of human diet intervention studies will help to clarify the role of interaction between diet and intestinal flora in human health and disease. Through dietary intervention to form or rebuild a reasonable intestinal flora structure, to provide ideas and methods for the prevention and treatment of related diseases.


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