commensal bacteria


An endless fight against ourselves: the IBDs.

The inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. Crohn’s disease and ulcerative colitis are the principal types of inflammatory bowel disease. 

  • Crohn’s disease may affect any part of the gastrointestinal tract from mouth to anus. Symptoms often include: abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever and weight loss. Other complications may occur outside the gastrointestinal tract and include: anemia, skin rashes, arthritis, inflammation of the eye, and tiredness. During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohn’s disease; it shows a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall. There is usually an abrupt transition between unaffected tissue and the ulcer - a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils into the epithelium. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with mononuclear cells, may infiltrate the crypts, leading to inflammation (crypititis) or abscess (crypt abscess). Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn’s disease. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (metaplasia). Cytokine response is associated with Th17. Terminal ileum is commonly involved, colon is usually involved, rectum is rarely involved. Stenosis is common. Bowel obstruction also commonly occurs (due to stenosis).
  • Ulcerative colitis is a form of colitis, a disease of the colon, that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset. Ulcerative colitis only attacks the large intestine and it is an intermittent disease, with periods of exacerbated symptoms, and periods that are relatively symptom-free. Although the symptoms of ulcerative colitis can sometimes diminish on their own, the disease usually requires treatment to go into remission. Endoscopic findings in ulcerative colitis include the following: loss of the vascular appearance of the colon; erythema (or redness of the mucosa) and friability of the mucosa; superficial ulceration, which may be confluent; pseudopolyps. Biopsies of the mucosa are taken to definitively diagnose UC and differentiate it from Crohn’s disease, which is managed differently clinically. Microbiological samples are typically taken at the time of endoscopy. The pathology in ulcerative colitis typically involves distortion of crypt architecture, inflammation of crypts (cryptitis), frank crypt abscesses, and hemorrhage or inflammatory cells in the lamina propria. In cases where the clinical picture is unclear, the histomorphologic analysis often plays a pivotal role in determining the diagnosis and thus the management. By contrast, a biopsy analysis may be indeterminate, and thus the clinical progression of the disease must inform its treatment. The degree of involvement endoscopically ranges from proctitis or inflammation of the rectum, to left sided colitis, to pancolitis, which is inflammation involving the ascending colon. Terminal ileum is rarely involved, colon is usually involved, rectum is always involved. Stenosis is rare. Cytokine response is vaguely associated with Th2.

Causes: while the exact cause is unknown, IBD seems to be due to a combination of environmental factors and genetic predisposition. It is increasingly thought that alterations to enteral bacteria can contribute to inflammatory gut diseases. IBD affected individuals have been found to have 30-50 percent reduced biodiversity of commensalism bacteria. Further evidence of the role of gut flora in the cause of inflammatory bowel disease is that IBD affected individuals are more likely to have been prescribed antibiotics in the 2-5 year period before their diagnosis than unaffected individuals. The genetic contribution is poorly understood and seems to arise from the small contribution of dozens of genes. In 2012 163 IBD susceptibility loci were confirmed which means that 163 alleles that can increase the susceptibility to the disease.

TreatmentMesalazine is more useful in UC than in CD. Antibiotics are effective in long-term in CD, but generally not useful in UC. Depending on the level of severity, IBD may require immunosuppression to control the symptom. Often, anti-inflammatory steroids are used to control disease flares. While ulcerative colitis can be treated by performing a total colectomy (removing the entire large intestine), surgery for Crohn’s disease involves removing the damaged parts of the intestine and reconnecting the healthy parts, which does not cure Crohn’s, as it can recur after surgery, mostly at the site of the intestinal anastomosis (connection) or in other areas. 

soundofaspark  asked:

Hello, I'm a huge fan! Your posts are cool and helpful. I became interested in immunology when I was diagnosed with Rheumatoid Arthritis (and Crohn's disease) I have taken several anti-TNF biologics. Could you please illustrate how they work? Thanks!

Thank you for the compliments!

The pathogenesis of Crohn’s disease and rheumatoid arthritis is complex. If  I were to over simply it, I’d think of the disease as a type IV hypersensitivity in which the body is reacting to self antigens in rheumatoid arthritis and commensal bacteria in Crohns disease.

One of the principal cytokines secreted by activated macrophages is TNF-a. TNF-a is an inducer of a local inflammatory response that helps to contain infections.

Think of TNF-a as a key. It’s unlocks the door to many inflammatory processes, some of which may be harmful. Think of TNF-a receptor as the key hole.

Some anti-TNF biologics like Infliximab bind to the key and make them look funny! This prevents the effective binding of TNF-α with its receptors.

Other anti-TNF biologics such as Etanercept look like the key hole. They bind to it and prevent TNF-a to bind to the real key hole. It reduces the effect of naturally present TNF, and hence is a TNF inhibitor, functioning as a decoy receptor that binds to TNF. This is what complex terms like “soluble proteins that mimic the receptor” mean.

Tried my best not to make the explanation too science-y!

I hope that your treatments go well =)

Asymptomatic colonization by Clostridium difficile, absent the use of antibiotics, is common in infants and when it happens changes occur in the composition of the gut microbiota, according to research published in the March 2011 issue of the Journal of Clinical Microbiology.

The adult human gut is an ecosystem containing several pounds of bacteria, including hundreds of species and more than 100 trillion (100,000,000,000,000) individuals. A healthy microbial ecosystem protects the host against Clostridium difficile, which frequently colonizes the gut after its ecological balance has been disrupted by broad spectrum antibiotics, says Anne Collignon, of the University Paris Sud, Chatenay-Malabry, France.