Understanding a Hidden Metabolic Organ, Term Paper Example

Introduction

The article by Couturier-Maillard et al (2013) explores how the absence of NOD2 exposes mice to colorectal cancer and colitis. The authors are able to demonstrate that the volatility of gut microbiota, also referred to as dysbiosis can lead to common intestinal diseases such as Krohn’s Disease (CD). They hypothesize that dysbiosis caused by the deficiency of NOD2 is communicable in mice, but is a reversible condition. The lack if NOD2/RIP2 leads to a proinflammatory surrounding that increases the likelihood of epithelial dysplasia in case of a chemical-induced injury. The authors also hypothesize that this condition can be treated by administering antibiotics or antibodies that neutralize interleaukin-6. They use laboratory mice to create a model that shows the importance of NOD2 in generation a defensive layer of microorganisms. These research findings are of clinical importance because they can offer solutions in the management of intestinal diseases.

Summary

The mice used in the study were exposed to chow diet and the following procedures performed: a mixture of gentamicin, bacitracin, streptomycin and ciprofloxacin was administered; 1 mg MR16.1 was injected to facilitate neutralization; and Coloview high-resolution endoscopy carried out. (Couturier-Maillard et al., 2013).

Recolonization.NOD2+ mice were produced and moved to autoclaved and germ-free microisolator enclosures prior gavages with fecal homogenates. The remainder of the homogenates was frozen to be processed later to determine the presence of bacteria. Microarray analysis was conducted on samples collected from the colon to determine gene expression. Additional procedures such as histopathological, immunohistochemistry, and FACS analysis were conducted on the colony specimens.

The researchers found that NOD2/RIP2 deficiency gives a maternally transmissible colitis risk to immunocompetent hosts. The researchers had hypothesized that transmission of disease-predisposing bacterial communities from generation to the other could cause the missing heritability in Crohn’s Disease.

Another significant finding from the study is that fecal dysbiosis in nod2-defeicient mice sensitizes the colonic mucosa to chemical harm. The researchers were able to demonstrate that responses to elements of microbiota from either NOD2- or RIP2 deficiency did not cause rapid colitis. This means that nod2-mediated dysbiosis limited the coordination of the expression of molecules needed for the integrity of the colonic epithelium that causes enhanced intestinal inflammation in response to injury.

Another significant finding was the communicable risk of intestinal diseases in the absence of NOD2 and RIP2. By studying single-housed and co-housed mice, the researcher determined that deficiency in nod2 and rio2 was associated with maternally transmissible microorganisms that seem to sensitize the intestinal mucosa to both colorectal-associated cancer and colitis. Lastly, the researchers found that treatment with broad-spectrum antibiotics decreased bacterial counts, disease severity, and immune cell trafficking and inflammatory reactions in NOD2-deficient organisms (Couturier-Maillard et al, 2013). The researchers concluded that manipulation of dysbiosis could be a potential therapeutic approach in managing intestinal disorders in humans.

Analysis

The conclusions made by the researchers are based on sound experimental approaches. By developing hypotheses and conducting experiments to prove them, the researchers can demonstrate the potential of manipulating the dysbiosis in treating intestinal disorders in humans. Findings from other studies are in line with the findings contained in this article. Strong evidence linking intestinal microbiota to disease pathogenesis is derived from studies that utilize germ-free mouse models of human autoimmune disease where the prerequisite for exposure to and colonization by microorganisms on disease commencement and progression can be determined (Guinane & Cotter, 2013). As shown by the research study reported in the article, the incidence or severity of the disease is lowered under germ-free conditions, which means that the microbiota is a trigger for disease progression.

The use of mice models studying human autoimmune diseases presents a significant challenge in understanding the precise role of the composition of gut bacterial communities in the development of gut intestinal disorders. Due to inter-species and intra-species variations in the composition of the intestinal mucosa, it is hard to determine accurate relations between human intestinal disorders and intestinal microbiota (Guinane & Cotter, 2013). One observation in this study and other related studies is the failure to identify the members of the pathogenic microbiota of pathobionts that reproduce the effect of microbiota as a whole.

Conclusion

The findings in this research article are of clinical significance because the loss-of-function mutation of NOD2 is linked to an increased risk to Crohn’s Disease. Since elevated secretions of interleukin-6 characterize the colonic mucosa of patients suffering from the disease, it is evident that Crohn’s disease is caused by a deficiency of or mutations of NOD2. Interleukin-6 regulates the differentiation and endurance of epithelial cells by activating the related Janus Kinases. Injury triggers the secretion of interleukin-6 by dendritic cells, which implies that the increased secretion of interleukin-6 is a predictor of disease severity. The findings helps in the development of therapies that seek to restore the mutualistic relationships between the microbiota and the susceptible epithelial barrier in individuals suffering from intestinal disorders.

References

Couturier-Maillard, A et al (2013). NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Investigation Volume 123 (2): 700-711

Guinane, C.M., & Cotter, P. (2013). Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol; 6(4): 295–308.