The Essay On Human Microbiota's Implications In Gut Inflammatory Diseases.

Inflammatory bowel disease is a perfect example of gut-microbe disease. Inflammatory bowel disease can be described as the recurring, persistent, idiopathic, and a multifactoral gastrointestinal inflammation.

Whereas the two most common type of Inflammatory bowel disease are: Crohn’s disease and ulcerative colitis. In the Crohn’s disease it has been seen that the inflammation occurs along the gastro-intestinal tract.

While the in ulcerative colitis, the inflammation is restricted only to the large intestine. The incidence of the gastro-intestinal inflammation is due to the imbalances in the population of the gut microbes.

The gastrointestinal cells are protected by a mucus covering and it consists of the mucus glycoproteins which is synthesized by the goblet cells.

These goblet cells get directly affected by the release of bioactive factors mucus are secreted during the process of fermentation by the microorganisms that are beneficial. The intestinal microbes have the potential to directly affect the goblet cells and it led to gut inflammation diseases.

Types of Inflammatory Bowel Disease

The human gut micro biota plays a major in the wellbeing of the human host and the diverse nature of the microbes is both beneficial and harmful for the humans. The most common microbes that are found to be interacting with the human immune system are the eukaryotes, viruses and bacteria and this plays an influential role in the development of diseases. Studies have indicated that a human body harbors about 100 trillion microbial cells. Thus, it is no denying that the human microbiota plays a decisive role in the both the maintenance of health and development of diseases (Scher et al. 2015). The microbiota is described to be involved in the harvesting of energy and its storage though a variety of metabolic functions which includes the absorption of undigested carbohydrates and fermentation of the undigested food. Thus, the evolutionary process played a key role in establishment of the microbes as human symbionts. However, one of the important aspects of human microbiota is the interaction of the microbiota with the immune system. The human microbiota helps in the signaling and promoting the maturation of the immune cells and the development of the immune functions (Kostic, Xavier and Gevers 2014). This study is based on the implication of human microbiota on the gut inflammatory diseases.

Identification of the healthy microbiota requires the proper designation of the microbial variability, which is a prerequisite and is a deviation from the disease states. Majority of the microbes reside on the human body and is exposed to the environment, whereas a larger section of the microbes resides in the intestinal tract. Microbial communities are found on the skin, in the vagina, and in the mouth. Bacterial communities that reside in similar sites of the body resemble in their characteristics. The microbes that are found in the mouth are similar in comparison to the microbes that are found in the mouth and skin surface. Especially the gut microbiota is dominated by the specific members like Firmicutes and Bacteroidetes (Lynch and Pedersen 2016). There is a huge difference between the taxa present in the gut and the microbial composition of individual microbes. The most common microbiota that are found in the human gut are the enterotypes and it consists of the Ruminococcus or Prevotella and Bacteroides. These microbial compositions are generally driven by the by the dietary effects. Studies have indicated that the dietary composition has significantly impacted the human microbiota. Also, the diet has a positive relation with the enterotype. It has been seen that the diet with high quantity of animal fat have the enterotype dominated by Bacteroides. However, in carbohydrate rich diet the diet is associated with the enterotype dominated by Prevotella. Gut inflammatory disease is also termed as crohn’s disease. This disease is characterized by the chronic gastrointestinal disorder and it results in to an inflammatory response in the intestinal mucosa. There are studies that highlight how the microbiota, genome and virome plays a role in interacting with the development of the crohn’s disease (Shreiner, Kao and Young 2015).

Role of Gut Microbes in Gastrointestinal Inflammation

Microbiome and its metabolites in disease and health

There are two major clinical phenotypes with respect to intestinal bowel phenotype. The first one is the crohn’s disease and the second one is the ulcerative colitis. In humans, studies have show there is an increased biodiversity of the Enterobacteriaceae and Bateroides and less abundance of the Firmicutes (Clemente, Manasson and Scher 2018). Is has been seen that Roseburia hominis and Firmicutes prausnitzii are found to be producing butyrate and is thus known to produce the T_reg via the receptor of GRR43. Both the taxa are seen to be linked inversely with the ulcerative colitis and furthermore it has been seen that the Phascolarctobacterium is capable of producing propionate and it produces propionate in the presence of Paraprevotella and in turn this induces the T_regs. However, there are other pathobionts that are enhanced in the intestinal bowel diseases, and this includes the Heliobacter hepaticus, Proteus mirabilis, Klebsiella pneumoniae and Clostridium difficile, Prevotellaceae, Stenotrophomonas maltophilia, Rhodococcus, Shigella and Escherichia coli (Liang et al. 2018). The dysbiotic shift is found to be in the favor of pathobionts and this contributes positively to the perturbations and affects the immune function of the lamina propria cells, which ultimately results into the inflammatory response and progress of the disease. Survey’s carried out on the microbiome of several patients have shown that the Fusobacteriaceae, Neisseriaceae, Veillonellaceae, Pasteurellaceae, Clostidiales, Bacteriodales, Enterobacteriaceae are found to be exhibiting a positive correlation with the disease. However, Coprococus, Ruminococcus, Blautia, Roseburia, Faecalibacterium, Bacteroides, Ruminococcaceae, Lacnospiraceae are found to be negatively coorelated with the biopsy samples that are collected from rectum and ileum. While excess exposure to the antibiotics increase the microbial dysbiosis. Specifically, the bacteria that are coated with the IgA increases the susceptibility of a human to gut inflammatory disease (Wang et al. 2017).

Inflammatory bowel disease is a perfect example of gut-microbe disease. Inflammatory bowel disease can be described as the recurring, persistent, idiopathic, and a multifactoral gastrointestinal inflammation. Whereas the two most common type of Inflammatory bowel disease are: Crohn’s disease and ulcerative colitis. In the Crohn’s disease it has been seen that the inflammation occurs along the gastro-intestinal tract. While the in ulcerative colitis, the inflammation is restricted only to the large intestine. The incidence of the gastro-intestinal inflammation is due to the imbalances in the population of the gut microbes. While studies have indicated that the large number of the Inflammatory bowel disease occurs due to the gut dysbiosis and the increased gut pathogenesis (Nagao-Kitamoto et al. 2016a). The evidences of dysbiosis is commonly observed in the intestinal bowel disease with the reduction in the population of the Faecalibacterium prausnitizii, Firmicutes sp. and Roseburia sp. These bacteria are found to play a major role in the in reducing the anti-inflammatory responses along with the reduction in the pro-cytokines. Besides it is also important to mention that the Faecalibacterium prausnitizii, Firmicutes sp. and Roseburia sp produces the butyrates that acts as an energy substrate for the colonocytes. Thus, it can be said that if the Faecalibacterium prausnitizii, Firmicutes sp. and Roseburia sp population in the gut reduces then there is a chance of increasing local inflammation. The Firmicutes are found to be the important regulator of mucosal immunity. Another highlighting fact came forward through the studies is the overall increase in the population of the Bacteroides fragilis and Enterobacteriaceae both have a high level of endotoxic LPS on their external membrane. Researches have shown that the high level of endotoxic LPS that are expressed by microbiota is shown to increase gut inflammation and the development of the colitis in mice. This occurs either through the activation of the effector Helper-T or by the suppression of the regulatory T-Lymphocyte and it takes place by the TLR4 signaling pathway (Kho and Lal 2018) (appendix 1).

The Impact of Human Microbiota on Health and Disease

It is a well-established fact that microbial biota plays a major role in the resistance towards the pathogenic microorganism and augments the intestinal epithelium. It has been found that the intestinal epithelial cells have the requisite places of contact for the microbial biota that acts to prevent the systemic translocation of substances. Intestinal epithelial cells have the lymphoid cells associated with the gut (GALT). GALT is rich in adaptive and innate immune system that helps in maintaining the gut homeostasis. GALT interacts with the intestinal cells and recognizes the pathogenic bacteria through the pattern recognition method. The patter recognition methods employed are the Nucleotide binding oligomerization domain (NOD) and Toll like receptors (TLRs). Studies have shown that the innate immune receptors have the proper structures that can identify both the commensal bacteria and pathogenic bacteria (Bernstein and Forbes 2017). While, it is important to mention a vital and important relationship exists between the commensal bacteria and intestinal epithelium and the relationship between the intestinal microbes and the human host is found to be healthy and symbiotic in nature. Thus, when the symbiotic relationship gets disrupted due to the alterations and interactions, there is a huge probability of the occurrence of dysbiosis, this promotes diseases state and human health is negatively affected. The gastrointestinal cells are protected by a mucus covering and it consists of the mucus glycoproteins which is synthesized by the goblet cells (Boulangé et al. 2016). These goblet cells get directly affected by the release of bioactive factors mucus are secreted during the process of fermentation by the microorganisms that are beneficial. The intestinal microbes have the potential to directly affect the goblet cells and it led to gut inflammation diseases. There are several diseases that are associated with the gut microbiota and the imbalances leads to the vaginosis, antibiotic associated diarrhea, tropical enteropathy, IBS, chronic periodontitis, inflammatory bowel disease and obesity. Both the increase and decrease in the number of the gut microbes is seen to be associated with the inflammatory bowel disease (Bakhtiar et al. 2013) (appendix 2).

When probiotics is considered, the Bifidobacterium and Lactobacillus are the two most beneficial for the human health. In children, Lactobacillus is known to prevent antibiotic associated diarrhea and at the same time prevents the growth of Lactobacillus rhamnosus GG and is also seen to prevent the growth of Helicobacter Pylori. Similarly, Bifidobacterium lactis is capable of promoting the human responses towards the human rotavirus. At least 9 different species of Bifidobacterium are identified to be commonly associated with the human gut (Clemente et al. 2012). Studies have shown that during a pathological condition of irritable bowel syndrome, inflammatory bowel disease and colorectal cancer, there is significant increase or decrease in the number of the Bifidobacterium in the human gut in comparison to the other microbes. Bifidobacterium is found to be interacting with cells of the intestine and this helps in inflammatory gene expression and immunity regulation. Studies have shown that the Bifidobacterium longum is capable of regulating the IL-1 alpha expression and regulation of the TNF-alpha in the patients that are suffering from the ulcerative colitis (Appendix 3). Even research in this field have shown that the probiotics has its usage in arenas other than the conventional reduction of harm. Microbial transplantation is one such method that enhance the therapeutic efficiency and the restoration of the gut microbes through transplantation to counter the Clostridium difficile colitis (Jin, Zhang and Sun 2014).

Identification of Healthy Microbiota

Conclusion

From the above discussion it can be concluded that the most common microbes that are found to be interacting with the human immune system are the eukaryotes, viruses and bacteria and this plays an influential role in the development of diseases. Studies have indicated that a human body harbors about 100 trillion microbial cells. Thus, it is no denying that the human microbiota plays a decisive role in the both the maintenance of health and development of diseases. microbial compositions are generally driven by the by the dietary effects. Studies have indicated that the dietary composition has significantly impacted the human microbiota. Also, the diet has a positive relation with the enterotype. It has been seen that the diet with high quantity of animal fat have the enterotype dominated by Bacteroides. Identification of the healthy microbiota requires the proper designation of the microbial variability, which is a prerequisite and is a deviation from the disease states. Majority of the microbes reside on the human body and is exposed to the environment, whereas a larger section of the microbes resides in the intestinal tract.

References

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