Introduction
Inflammatory bowel disease is an auto-immune condition. An autoimmune condition is one where the body’s immune system attacks its healthy cells. The factors that trigger this or cause the condition are still unknown. Research is ongoing to find the exact cause and the impact of genetics, environment, and other factors behind the condition. Prolonged inflammation can cause harm to the gastrointestinal tract.
What Is Inflammatory Bowel Disease?
Inflammatory Bowel Disease (IBD) is a recurrent illness that causes chronic inflammation in different parts of the gastrointestinal tract. It is a broad term for ulcerative colitis and Crohn’s disease. A cell-mediated immune response in the mucosa of the gastrointestinal tract causes inflammation. Although the exact cause of inflammatory bowel disease is uncertain, research points to patients who have a complex genetic predisposition having normal gut flora that unintentionally activates an immune response. There are no known nutritional, environmental, or viral causes. Tumor necrosis factor, interleukins, and cytokines are among the inflammatory mediators released during the immunological response.
What Is the Role of Microbiome in Inflammatory Bowel Disease?
The intestinal barrier can become dysfunctional in IBD patients due to a combination of endogenous (genetic) and exogenous (genetic, microbial, dietary, and stress) factors that increase the permeability of the intestinal mucous layer and intestinal epithelium. This facilitates the translocation of micro-organisms and products of microbial origin from the intestinal lumen into these tissues. This, in turn, triggers the activation of immune cells, a Treg imbalance, and the production of cytokines. All of these contribute to the development of chronic inflammation. Consequently, the persistent inflammation exacerbates the pre-existing breaches in the barrier function.
It is assumed that in conditions of microbial homeostasis, symbiotic microorganisms have a predominantly anti-inflammatory effect by suppressing pathobionts characterized by a potential colitogenic effect by inducing an immune response involving intestinal regulatory T cells (Treg), and anti-inflammatory interleukin IL-10. This is one way in which the intestinal microbiota may contribute to developing and maintaining the inflammatory process in the intestine. In IBD, a mix of hereditary and environmental variables leads to intestinal dysbiosis, or disruption to the structure of the microbiota, as well as an imbalance in the intestinal mucosa's barrier function. An increase in pathobionts, indicative of a dysbiosis state, and a decrease in ‘protective’ symbiotic bacteria both contribute to and worsen the inflammatory process. The activation of pro-inflammatory T-cells (Th17) in genetically susceptible people may be enhanced by an increase in pro-inflammatory bacteria, leading to a Th17-mediated autoimmune response. Consequently, a decrease in the quantity of anti-inflammatory microorganisms may cause a particular group of important immunoregulatory cells (Treg) to fail to develop. At some point, autoimmune inflammation will arise due to an imbalance between Th17 and Treg.
How Do Gastrointestinal Pathogens Increase the Risk of Inflammatory Bowel Disease?
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Bacteria: Many studies point out that bacteria can be a potential trigger in IBD. Several association studies implicate Salmonella species, Clostridium difficile, Enterohepatic Helicobacter Species (EHS), Mycobacterium Avium Paratuberculosis (MAP), Campylobacter species, and Listeria monocytogenes, even though no single causative microorganism or related time course has been identified.
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Campylobacter Species: Concerning its virulence-associated restriction-modification system, C. Concisus, in particular, is capable of various pathogenic activities, such as adhering to and invading host cells and secreting toxins. In one investigation, deoxyribonucleic acid (DNA) and antibodies against C. concisus were found much more frequently in patients with Crohn’s disease than in those without IBD. Compared to individuals without Crohn’s disease or ulcerative colitis, a study on adults showed that C. concisus DNA was found far more frequently in colonic biopsies of patients with Crohn’s disease and ulcerative colitis. Several further minor investigations that used intestinal biopsies from patients with Crohn’s disease and ulcerative colitis and used polymerase chain reaction and culture techniques validated these findings.
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Salmonella Species: Compared to patients without gastroenteritis, a gastroenteritis episode resulting in a stool culture positive for Salmonella species was substantially linked to an elevated risk of new-onset ulcerative colitis and Crohn’s disease. Although with effect estimates of slightly lower magnitude of effect, the more recent statewide case-control study from Sweden, also cited above, also showed a positive relationship between a Salmonella diagnosis and IBD risk.
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Enterohepatic Helicobacter Species: Certain strains of Enterohepatic Helicobacter have been linked to the onset of IBD in humans. Compared to non-IBD controls, patients with Crohn’s disease had more frequent intestinal biopsies with Helicobacteraca DNA in research.
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Clostridioides Difficile: Research has examined the relationship between IBD and C. difficile infection. However, the analysis of Clostridium infection as a risk factor for newly diagnosed IBD is extremely limited. Emerging evidence also points to genetic factors, even if the decreased diversity of bacterial species in IBD may put people at risk for colonization by C. difficile.
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Viruses: There is little evidence to support viruses as risk factors for IBD in vulnerable individuals. The viruses that are easiest to screen for are the ones that have been studied the most. The involvement of norovirus, cytomegalovirus, Epstein bar virus, and Human herpes virus-6 in the pathogenesis of the disease, their correlation with flare-ups, complications, and response to treatment, and their relative prevalence in the general population are still unknown. The impact of exposure timing and other modifying factors must be determined through carefully planned prospective studies with sufficient control populations.
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Fungi: Recent technological developments have made it possible to characterize previously unknown gut microbiome members in greater detail. These individuals may also be crucial to the pathophysiology and progression of IBD. Recent research employing high-throughput sequencing techniques shows that fungal diversity is different in ileal and colonic biopsies from CD patients as opposed to healthy controls. In particular, several investigations have shown that different amounts of the gastrointestinal pathogenic species of Aspergillus, Candida, Malassezia, and Cryptococcus neoformans are present.
Do Gastrointestinal Pathogens Play a Role in the Relapse of IBD?
Gastrointestinal tract infections are commonly associated with relapses of previously diagnosed IBD. Given the striking similarities between the clinical presentation of an intestinal infection and an IBD flare, these conditions may coexist or are separate from one another, which would make determining causality and interpretation more challenging. Current clinical guidelines recommend testing for C. difficile and CMV in all IBD patients who are experiencing diarrhea, whether it is new or getting worse. This is crucial if the patient takes steroids on the side and their condition is not improving with medicine. An essential component of both IBD and infectious diseases is an impaired intestinal barrier. A recent study found that intestinal permeability predates the diagnosis of CD, indicating a potential role for pathogen-induced disruption of the barrier.
Conclusion
In conclusion, gastrointestinal infections caused by bacteria, viruses, and fungi can alter a patient's risk of developing IBD. They can also cause flare-ups or make them more difficult for those who already have the disease to manage. It is not possible to definitively establish a direct causal relationship between gastrointestinal infection or colonization and new onset or flare-up of IBD.
