Journal of Applied Pharmacy
Open Access

Importance of Antibiotic Use: Enhancement of Gut Permeability by Pancreatic Enzymes

Katherin Narin^{* *}Correspondence: Katherin Narin, Department of Chemistry, Osaka University, New York, USA, Email:

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Description

We are beginning to understand the dangers of mediating the microbiome with broad-spectrum antibiotics as we learn more about the significance of this system in inflammatory, metabolic, and functional problems. Antibiotics have significantly decreased the danger of infectious diseases, but we've known for a long time that other disorders including inflammatory bowel disease, obesity, and type 2 diabetes mellitus have become more common. Antibiotic exposure substantially doubles the incidence of Crohn's Disease (CD), despite the fact that the causes are probably multifaceted. The current study provides one possible mechanism where antibiotic exposure doubles the incidence of Crohn's Disease.

Patients who gave stool samples both before and after taking a variety of antibiotics were the subject of the authors' study. They discovered that faecal protease activity had significantly increased in 8 individuals. When applied to a polarized monolayer of cultivated colonic epithelial cells, faeces with higher protease activity increased permeability.

Although this was considerably less clear after receiving antibiotics like rifaximin, which have less of an effect on the microbiota, this was particularly noticeable in patients given antibiotics like levofloxacin and metronidazole, which are known to significantly diminish faecal microbiota. The pancreas secretes over 500 mg of tryptase into the gut every day, but only about 1 mg is eliminated. Early animal trials have demonstrated that broad-spectrum antibiotics largely block this breakdown.

Using cell lines and animal models, this research investigates the effects of antibiotic-induced enhanced faecal proteases on gut barrier function. They demonstrated that pancreatic serine proteases like trypsin and chymotrypsin increased with the use of broad-spectrum antibiotics (vancomycin and metronidazole) in mice. This caused permeability to increase, which in healthy wildtype mice lasted for around 14 days but did not cause an inflammatory reaction. However, repeated antibiotic treatments cause the development of a chronic colitis in genetically vulnerable interleukin 10 knock-out mice. This condition could be prevented by a particular protease inhibitor although CD is severe, it is usually rare, and the majority of antibiotic courses do not result in the development of CD. Irritable Bowel Syndrome (IBS) is approximately 100 times more common, affecting approximately one in every ten people. Antibiotic use is also linked to IBS, with a threefold increase in the risk of developing functional gastrointestinal symptoms in the four months following antibiotic use. IBS with Diarrhoea (IBS-D), characterized by rapid colonic transit and gut hypersensitivity to distension, is associated with increased faecal proteases.

Furthermore, in animal studies, IBS-D faecal supernatants were shown to sensitize murine colons to distension via proteaseactivated receptor type 2, implying that faecal proteases may account for visceral hypersensitivity. Because the effect demonstrated in this study was temporary, it cannot cause an inflammatory response in normal animals, the studies explain that in genetically susceptible individuals, it could start a selfperpetuating cycle of increased permeability, allowing access of microbial antigens, leading to immune activation, which in turn increases permeability.

Several studies have discovered significant changes in gut microbes in CD and IBS-D, which have been linked to mucosal activation of inflammatory genes. The effect of antibiotics shown in the current study supports the idea that an altered gut microbiota might be an important part of the pathogenesis of both conditions. However, not all bacteria degrade proteases so specifically examining whether the altered microbiota in these diseases has impaired protease degradation would be a logical next step.

Gastroenterologists perhaps are more aware than most doctors through their experience in treating Clostridium difficile of the risks of depleting the microbiota with broad-spectrum antibiotics, and new better-targeted agents are being developed to treat this condition. However, most antibiotics are given for nongastrointestinal infections and, until recently, their impact on gut microbiota largely was accepted as inevitable. The current study provides an important reason why we should be developing more specifically targeted antibiotic.