As more and more research sheds light into the darkness of our colons with their billions of bacterial residents living there, we learn more and more how those bacteria interact with our immune system leading to inflammatory bowel diseases like Crohn’s Disease. We need these little critters inside our GI tract to provide a number of functions between digestion, vitamin production, and immune system stimulation. Having a good mix of these bacteria combined with an appropriate immune response keeps both our GI tract and our immune system in good working order. It appears that dysfunction of this interaction between 2 types of bacteria and an antibody known as IgG subclass 2 may play a role in severe Crohn’s disease.
As the number of people suffering from autoimmune diseases increases, a GI focused autoimmune disease called Crohn’s disease afflicts at least 500,000 people in the US (1). In this group of diseases called inflammatory bowel diseases, that also includes ulcerative colitis, the immune system turns against cells in the GI tract. The inappropriate immune response destroys cells and tissues of the GI system, leading to inflammation, dysfunctional tissues, ulcers along the GI tract, bleeding, malnutrition, pain, and much more. Understanding how the process proceeds offers hope to relieve the suffering of these patients.
Researchers from the Technical University of Denmark looked at how differences in antibody responses to specific gut bacteria might contribute to the severity of Crohn’s patients. They knew from prior research that our immune systems produce a variety of antibodies that coat the surfaces of different bacteria, controlling their growth and inflammatory potential. Most research looked at Immunoglobulin A, IgA, which is the primary antibody secreted from the mucosal surfaces lining our gut. Such secreted IgA protects us from bacteria or viruses before they can break through into our tissues from the food going through our system.
This paper describes the role of another antibody type called Immunoglobulin G in the inflammatory process underlying Crohn’s disease. This antibody type is produced in 4 subtypes, named 1 through 4. Through their research they found that the binding of subtypes 1 and 4 IgG for gut bacteria were basically the same in Crohn’s disease and those who were healthy. However, the levels of gut bacteria coated with IgG subtype 2 were much higher in Crohn’s patients. They were especially higher in those with severe Crohn’s disease.
Another interesting finding was that two particular bacteria were not coated by these IgG subtype 2 antibodies. Campylobacter and Mannheimia bacterial species appear to avoid this coating in the more severe cases of Crohn’s. They did not elaborate further on this correlation.
The researchers hope that this clearer understanding of how Crohn’s disease develops could lead to better treatment. On one hand, they foresee therapies that modulate this antibody binding in a way that decreases gut inflammation. On the other hand, they foresee that such a biomarker of high IgG subtype 2 or high levels of these two bacteria could help GI doctors predict which patients will proceed to more severe disease and thus deserve more aggressive therapy.
For functional medicine providers, it reminds us of the critical nature of the gut-immune-microbiome interplay. Leaky gut and dysbiosis (imbalance in gut bacteria) are now well-known contributing factors to autoimmune diseases affecting the entire body. Research like this study should not surprise us that the same factors would play a role in autoimmune diseases in the gut itself. In helping patients restore healthier, more abundant lives, we will continue to work on gut health, lowering inflammation, balancing the gut microbiome, and using natural therapies to optimize gut health while minimizing autoimmune risks.
Original Article:
Carsten Eriksen, Niels Banhos Danneskiold-Samsøe, Janne Marie Moll, Pernille Neve Myers, Pi W Bondegaard, Simone Vejrum, Tine Brodka Hansen, Lisbeth Buus Rosholm, Philipp Rausch, Kristine Højgaard Allin, Tine Jess, Karsten Kristiansen, John Penders, Daisy Jonkers, Susanne Brix. Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn’s disease. Gut, 2024; 73 (3): 448 DOI: 10.1136/gutjnl-2023-330677
Thanks to Science Daily:
Technical University of Denmark. “New understanding of the gut immune system may hold promise for Crohn’s disease patients.” ScienceDaily. ScienceDaily, 15 March 2024. <www.sciencedaily.com/releases/2024/03/240313135452.htm>.
Additional Citation:
[1] Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured U.S. population. Digestive Diseases and Sciences. 2013;58:519–525.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.
