Nature ReviewsThe role of the Troika in colitis rehabilitation

Mondo Health Updated on 2024-02-21

Nature Reviews Microbiology, a top academic journal published a new year article, which comprehensively reviewed the role of intestinal microbes in inflammatory bowel disease (IBD), summarized the research results related to the pathogenesis of IBD, and revealed the characteristics and differences between healthy people and IBD patients in microbial flora and related metabolites. Exhaustive references are provided.

It has been clinically proven that the intestinal flora plays a pivotal role in human health: it controls 70% of the body's immunity, eliminates 80% of toxins, digests and absorbs 95% of nutrients, and is the connector of the entire metabolic system of the human body.

With the development of the human microbiome program, the imbalance of the intestinal microbiota has been directly or indirectly related to more than 50 diseases, including tumors, digestive diseases (such as inflammatory bowel disease, chronic diarrhea), immune system diseases, metabolic diseases, and psychiatric diseases. Among them, the research on inflammatory bowel disease is one of the earliest and most fruitful fields. Inflammatory bowel disease includes ulcerative colitis (UC) and Crohn's disease (CD), with the main symptoms being: intermittent abdominal cramps and bloody diarrhea, chronic diarrhea, and abdominal pain.

According to the statistics of the Chinese Center for Disease Control and Prevention, it is expected that by 2025, the total number of IBD patients in China will exceed 1.5 million.

The high incidence of inflammatory bowel disease is closely related to environmental pollution and industrial pollution, in addition, host genetics, smoking, diet, drugs**, staying up late, fatigue and stress, as well as a large number of free radicals produced, will also affect the beneficial intestinal flora, and then reshape our immune system to a certain extent, inducing or aggravating inflammatory bowel disease.

Studies have shown that caesarean sections, non-breastfeeding, overly clean living, urbanization, and antibiotic misuse may lead to a lack of exposure to microbes in young children early in life, leading to a more "sensitive" and "inflamed" gut. In particular, early childhood exposure to antibiotics is associated with an increased risk of inflammatory bowel disease.

In addition, the intestinal microbe, as the "connector of the human metabolic system", can also "turn on the green light", so that the inflammation that originally only existed in the intestine can "flow unimpeded" throughout the body and metastasize to other body parts (such as joints, eyes, oral cavity and **), resulting in inflammation in other parts and even leading to cancer.

01 How do microbes affect our immune system?

The immunoregulation of the "bacterial membrane barrier" composed of beneficial bacteria in the gut mainly includes three aspects.

First of all, the large number of microbiota present in our intestinal epithelial mucosa, as well as the mucus and cells in the intestinal epithelium, constitute a physical barrier, which provides the first layer of protection for the symbiotic relationship between the intestinal microbiota and the host.

Secondly, our gut can also secrete antimicrobial peptides to give a "magic attack" to intestinal invaders, a chemical barrier that is the second layer of protection for the symbiotic relationship between the gut microbiota and the host.

Finally, humoral immunity, represented by immunoglobulin IgA, provides a third layer of protection. Studies have shown that it plays an important role in the prevention of autoimmune and inflammatory diseases.

Patients with inflammatory bowel disease have an imbalance in the intestinal microbiota and defects in epithelial cells. At the same time, the intestinal microbiome barrier is disrupted, and the level of short-chain fatty acids will be further reduced, further aggravating the condition. Studies have shown that supplementing with Huojun No. 1 patented strain can help reconstruct and repair the bacterial membrane barrier on the surface of the intestinal mucosa, accelerate the healing of the inflammatory ulcer surface, and restore the health of intestinal mucosal epithelial cells.

02 What happens to the gut microbiome in inflammatory bowel disease?

1) Composition change.

Overall, the intestinal microbial diversity of patients with inflammatory bowel disease is reduced. These include a decrease in the abundance of firmicutes, the disappearance of Clostridium cluster IV and XIV species, and an increase in the abundance of Enterobacteriaceae. Some studies also observed changes in bacteroides, bifidobacterium, and lactobacillus. According to the current research results, blautia, faecalibacterium, ruminococcus are the key microflora in Crohn's disease and ulcerative colitis. Lachnospiraceae and ruminococcaceae are closely associated with disease, adverse effects of anti-tumor necrosis factor, and surgical intervention in patients with Crohn's disease.

Several large cohort studies of metagenomic sequencing of human stool samples showed that 219 taxa (152 species) at different taxonomic levels were associated with Crohn's disease, 102 taxa (93 species) were associated with ulcerative colitis, and 87 of them were present in both inflammatory bowel diseases.

Specifically, a significant decrease in Lachnospiraceae and Ruminococcaceae, as well as an increase in Enterobacteriaceae, were observed in Crohn's patients; In the case of ulcerative colitis, the decrease in bacteroidaceae and the increase in Lachnospiraceae are the main factors. In addition, a significantly reduced diversity of the beneficial bacteria faecalibacterium prausnitzii and roseburia intestinalis was observed in Crohn patients compared to healthy people, as well as Bacillus fragilis (B. fragilisFragilis) and Escherichia coli (Escherichia coli) growth rates increased. It is worth mentioning that the changes in the abundance of Escherichia and bacteroides are directly related to the increased abundance of resistance genes in inflammatory bowel disease.

2) Functional changes.

The microbiota function of patients with inflammatory bowel disease is also significantly different from that of healthy people. In particular, there are significant changes in functions such as the synthesis of amino acids, neurotransmitters and vitamins, the regulation of mineral absorption, and the degradation of complex carbohydrates. In a study of changes in the metabolic activity of the microbiota in inflammatory bowel disease, researchers found that there was a general loss of microbiota diversity in patients with inflammation, with 50 types of bacteria and 568 enzymes different.

3) Metabolite changes.

Several human studies have shown differences in metabolites in stool, serum, or mucous membranes in patients with inflammatory bowel disease compared to healthy people. In patients with ulcerative colitis, taurine and cadaverine levels are elevated, while changes in carnosine, ribose, and choline levels are associated with inflammation. Patients with inflammatory bowel disease have a similar microbiome to healthy first-degree relatives when they are not present.

0 3 How can understanding the changes in microbes help us?

Currently, about 50% of the differences in the composition of the microbiota in inflammatory bowel disease are observed between individuals. Clinical data show that less than half of patients with inflammatory bowel disease respond to the traditional ** strategy. In addition, inflammatory bowel disease is characterized by periodic episodes, with periods of remission. In view of the changes in the composition and functional characteristics of the intestinal microbiota in patients with inflammatory bowel disease, we can provide a more personalized and accurate plan.

Case in point: In the second phase of the Human Microbiome Project (HMP2), researchers followed 132 patients with inflammatory bowel disease and healthy people for a year, collected 1,785 stool samples, 651 intestinal biopsy samples, 529 quarterly blood samples, and conducted detailed health questionnaires.

The results showed that patients with inflammatory bowel disease had a more unstable microbiome, immune response, and metabolites than healthy people, and could even undergo "drastic" changes within a few weeks.

In other words, even in the same patient with inflammatory bowel disease, his intestinal flora changes from moment to moment as the course of the disease changes. And this, for healthy people, is almost impossible.

Therefore, to address the root causes of inflammatory bowel disease, it is necessary to restore a healthy balance of intestinal microbiota structure. Studies have found that supplementation with Huojun No. 1 patented strain, after 3 to 6 months, significantly helps to restore a healthy balance of intestinal flora structure.

0 4 What can we do with microbes in inflammatory bowel disease?

1) Filter the **plan** effect.

At present, there are many clinical ways to target inflammatory bowel disease, but most of them have a remission rate of less than 50%. Therefore, understanding a patient's microbial makeup can help them respond to a specific inflammatory bowel disease. For example, the combination of gut microbiota and other clinical factors can lead to a patient's response to anti-integrin, anti-tumor necrosis factor, or ustekinumab. While these findings have yet to be validated by more similar studies, it is undeniable that the gut microbiome has unique advantages and potential when it comes to choosing the best** regimen for patients with inflammatory bowel disease.

2) Fecal transplantation: 28% of ulcerative colitis achieved clinical remission.

Fecal microbiota transplantation (FMT), also known as fecal bacteria transplantation, refers to the transfer of feces from a healthy donor into a patient's intestine. This regimen has been highly effective in Clostridium difficile infection, with clinical remission in 28% of patients with ulcerative colitis in four randomized controlled trials. At present, a preliminary consensus has been formed on the use of fecal bacteria transplantation for ulcerative colitis**: antibiotics are required before fecal bacteria transplantation**; Inflammation is manageable, and controlling inflammation may lead to more efficient** results.

3) Alter the immune function of the host.

At present, effective probiotic strains have been successfully identified to alter the immune function of the host through the microbiota, such as: Lactobacillus reuteri JYLB-291 and Lactobacillus casei LCASEI21, Bifidobacterium longum JBLC-141, Lactobacillus paracasei JLPF-176, Lactobacillus acidophilus Jyla-191, Bifidobacterium adolescent BBF-06, etc., can regulate adaptive immune responses through microbial-derived metabolites or enzymes. In general, this type of ** is still in its early stages of development. As we gain a better understanding of the mechanisms by which specific microorganisms interact with the immune system, more targeted microbes may be developed in the future**.

0 5 The "Troika" of Inflammatory Bowel Disease

The first carriage: adhere to the drug **.

Although the intestinal flora plays a very important role in the disease, prevention and management of inflammatory bowel disease, the role of drugs is essential during inflammatory attacks, and it is also the most effective and direct plan to prevent the exacerbation of the disease. Drugs commonly used in ulcerative colitis are aminosalicylic acid preparations (sulfasalazine, mesalazine), hormones (prednisone, budonide), and immunologic agents (cyclosporine, thiopylatene), and if none of these three drugs are controlled, the biologic infliximab may be used. Drugs have strong drug resistance and dependence, and the dose, course of treatment and method of taking are strictly regulated, and must be used under the prescription of the hospital doctor, and the drug must not be used or stopped at will.

The second carriage: adhere to the intestinal flora regulation of specific probiotics.

There are thousands of probiotics, but only specific probiotics have a specific role in improving the structure of the inflammatory bowel disease flora, and the top star strain of Huojun No. 1 is Lactobacillus reuteri JYLB-291, which has obtained the Chinese invention patent number ZL 2021 1 15660790, the patent details of the publicity of the invention patent is true and effective, for ulcerative colitis caused by fecal mucosal pus and blood, abdominal pain, increased stool, loose stools, etc., the total effective rate can reach up to 957%, functional test results:

Secondly, the first star strain of Lactobacillus casei LCASEI21 also plays a prominent role in regulating the intestinal microbiota structure of IBD patients, and the academic literature "Effect of **Lactobacillus casei combined with conventional** on the short-term outcome of ulcerative colitis" concludes that Lactobacillus casei combined with conventional ** can effectively ** ulcerative colitis, significantly alleviate the clinical symptoms of patients, and has high safety, which is worthy of promotion and clinical reference. This strain obtained the China Invention Patent No. ZL 2021 1 02424785. The patent details are publicized for abdominal pain, diarrhea, frequent bowel movements, and lukewarm limbs caused by enteritis, with a total effective rate of up to 92% in 30 days, and the results of functional tests:

Third: Huojun No. 1 star strain Bifidobacterium longum JBLC-141 has a good effect on the recovery of IBD's autoimmune system, Professor Nie Shaoping of Nanchang University published "Bifidobacterium longum relieves colitis: the influence of different intestinal flora backgrounds" in the "Journal of Food Science", which pointed out that Bifidobacterium longum may be an effective ** or auxiliary ** means for ulcerative colitis. Patients with enteritis will produce a large number of free radicals in the body every day, free radicals are the source of all diseases, one of the main culprits of aging and tumors, free radicals attack normal immune cells to make it "abnormal", and then attack intestinal mucosal cells, which is one of the culprits of autoimmune diseases. The No. 1 star strain of Bifidobacterium longum JBLC-141 enhances the function of eliminating excess free radicals in the body, prevents the loss of free radicals to body cells, and can also play a certain role in protecting cell oxidative damage and relieving body fatigue, and has obtained China Invention Patent No. ZL 2021 1 0227019x。

According to the statistics of **Huojun No. 1 official enterprise store, IBD users insist on paying equal attention to the five troikas, and after taking Huojun No. 1 to regulate the intestinal flora structure for 3 to 6 months, more than 90% can embark on the road of **.

The third carriage: adhere to the health management of mental stress.

According to statistics, the overall prevalence of depressive symptoms in patients with IBD is 21% to 252%, and the overall prevalence of anxiety symptoms was 191%-35.1%。The prevalence of IBD with depressive and anxiety states in children was 15% and 16, respectively4%, and the prevalence of diagnosing depression and anxiety disorders was 3., respectively4% and 42%。

David Perlmutter, MD, revealed in "The Brain of the Flora" that the intestinal microbiota is involved in the regulation of the gastrointestinal nervous system, and acts on the brain through the brain-gut axis, interpenetrating each other, that is: long-term mental stress and unhealthy emotions will lead to frequent and extreme changes in the structure of the intestinal flora, inducing IBD; At the same time, if you have IBD, intestinal discomfort will act on the brain through the brain-gut axis, leading to unhealthy mental emotions such as anxiety, depression, and doubt. Supplementing with specific probiotics (Huojun No. 1) acts on the gut microbiome, helping to alleviate this mental stress conduction. However, it is essential for IBD patients to self-regulate or use psychological counselors to release mental pressure and eliminate anxiety, depression, irritability, doubt and other emotional activities.

The fourth carriage: adhere to the healthy management of dietary structure.

Currently, microbiome-based inflammatory bowel disease is mainly through suppression of the immune system and dietary changes; Among them, dietary changes are the most common, i.e., changes in the composition of microorganisms by adjusting nutritional availability. Overall, diet has a strong effect on the gut microbiome, and this effect is fairly rapid and unaffected by inflammation and antibiotics. Dietary patterns have been shown to be associated with the risk of inflammatory bowel disease.

At the same time, there are still many challenges in assessing the effects of diet on disease, such as the accuracy of dietary intake information, the complex interactions between foods consumed, and differences in food metabolism between individuals. In the future, it may be possible to modify the diet through engineering means to limit harmful ingredients, supplement beneficial nutrients, or combine with other ** to assist in disease prevention and **.

The role of diet in the aetiopathogenesis of inflammatory bowel disease was published in the journal Nat Revgastroenterol Hepatol, which explores the relationship between diet and the risk of inflammatory bowel disease from epidemiology, gene-environment interactions, microbial and animal studies. Primary outcomes include: Western-style diet (red meat, processed foods, refined sugars, saturated fats) is associated with an increased risk of inflammatory bowel disease; Possible mechanisms by which diet leads to inflammatory bowel disease, including causing intestinal dysbiosis, disrupting intestinal barrier function, and altering the ratio of pro-inflammatory Th17 cells to regulatory T cells (TREG); A Mediterranean diet, characterized by a high intake of fruits and vegetables, whole grains and seafood, can increase the diversity of intestinal flora, maintain intact intestinal barrier function, and balance the ratio of Th17 cells to TREG. Some prospective studies have found that linoleic acid, heme iron, etc. are associated with an increased risk of IBD, and DHA, dietary fiber, zinc, potassium, milk, etc. are associated with a reduced risk of IBD.

The journal "GUT" published "Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases", demonstrating the key role of diet in the pathogenesis and ** of inflammatory bowel disease, and the main results include: parenteral nutrition has been shown to alleviate symptoms in patients with Crohn; More than 4 weeks can reduce surgical intervention; Based on parenteral nutrition regimens, elimination diets that exclude specific ingredients, or specific probiotic foods, can alleviate inflammatory bowel disease and serve as a salvage after biological or combination failures; Dietary education for patients is commendable, and although it is still in its infancy, the use of dietary ** inflammation can bring clinical benefits.

Principles of healthy management of the dietary structure of IBD patients: Mainly warm, avoid eating raw and cold food, and avoid irritating the intestinal mucosa. Mainly liquid food, such as porridge, millet porridge, avoid greasy and indigestible food, increase the burden on the stomach. The diet should be as light as possible, avoid spicy and irritating food, aggravate congestion and inflammation, and poor hair discharge. Avoid gas-producing foods that cause discomfort such as abdominal pain. Avoid coarse foods, which may stimulate gastrointestinal peristalsis and increase the digestive burden of the intestines. Avoid seafood and avoid certain foreign proteins that can easily cause allergies and aggravate inflammatory reactions. Avoid foods that promote excretion and lubricate the intestines, as well as foods that contain lactose. Do not eat overnight food, stale or out-of-season food, salty food and preserved products. Avoid overeating, which will cause gastrointestinal disorders.

Troika 5: Adhere to lifestyle health management.

Lifestyle westernization, characterized by unhealthy eating habits and reduced physical activity, is not only associated with an increased incidence and prevalence of inflammatory bowel disease (IBD), but may also affect the course of the disease in patients with confirmed IBD. In addition to medications, many people with IBD seek support** and adjuncts**. They often consult their doctors for advice on diet and lifestyle to improve or even ** disease. Several studies have shown that various lifestyle factors, including diet and physical activity, play an impact on the course of the disease. A healthy lifestyle may help maintain remission and improve health-related quality of life (HRQOL).

IBD is also known as non-specific inflammatory lesions, which means that the global incidence of IBD and the big data of the world, as well as the medical community generally believe that IBD is related to microbiota factors, immune factors, environmental factors, mental factors, genetic factors and infectious factors, or the result of a joint effect, and the life and health management of IBD is to reduce the possibility of these factors. We must prohibit or avoid any lifestyle that leads to dysbiosis, reduced immunity, depressed mood, and disease infection.

Healthy lifestyle management includes: regular healthy eating, regular meals; Regular work and rest time, don't stay up late, don't get tired, go to bed early and get up early with lunch break, and maintain adequate sleep; Exercise properly, don't sit and stand for a long time, don't do strenuous exercise, maintain physical strength, you can walk or jog, Tai Chi or yoga, and rest in bed during bleeding; Keep the abdomen warm to prevent cold, prevent air conditioning in summer, and prevent body cold in winter. Be calm, do more things that make you happy, and keep smiling. For example: chatting, reading books, planting flowers, etc.

06 Conclusion.

Probiotics can help us shape and strengthen the immune system, resist pathogen colonization, maintain intestinal mucosal barrier function, and deeply participate in the regulation of host immunity. In these processes, it is not only a single probiotic that plays a role, but also mental emotion, dietary structure, lifestyle, etc.

At the same time, numerous studies have confirmed that inflammatory bowel disease is a complex disease influenced by a variety of factors such as host, microbiological, and environmental factors; The occurrence and development of diseases are indispensable for intestinal microbes. In clinical practice, there have been cases of remission of severe inflammatory bowel disease with antibiotics or remission of Crohn's disease in children by enteral nutrition; However, neither approach has been able to sustain remission or disease. Therefore, an in-depth understanding of the mechanisms of the aberrant interaction between the host immune system and the gut microbiota is of great significance for the development of effective methods, focusing on the five troikas, and ultimately defeating inflammatory bowel disease.

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