Dysbiosis and Inflammatory Bowel Disease
Microbial Solutions
Rana Samadfam, PhD

Dysbiosis and Inflammatory Bowel Disease

A microbial imbalance in the body seems to correlate with IBD, but does it actually cause it? Maybe, maybe not.

The human body as an ecosystem in which complex interfaces consolidate signals from hosts (bacteria and human) and microbiota (bacterial and phage), and activate appropriate effector programs, in order to maintain a delicate balance. This balance is continuously under assault by behavioral and environmental factors. What we eat, what medications we take, how much exercise we get, how much stress we experience, our hygiene, our exposure to infections, and our overall immune health creates disturbances in this balance.

If the assault is short-lived, our system is often able to recover and regain a healthy balance. If the assaults persist and multi-layer regulatory mechanisms fail to restore the ecosystem balance, the population and/or function of different players will shift toward a new norm that may not be in the best interest of the human host. This results in a condition called dysbiosis, a microbial imbalance or maladaptation of the body.

Dysbiosis and its link to IBD

Dysbiosis is associated with several diseases including obesity, diabetes, autoimmune diseases, skin diseases, dementia and inflammatory bowel disease (IBD), such as colitis. Among these diseases, IBD has gotten the most attention from dysbiosis researchers and clinicians, because the association between dysbiosis and IBD has been confirmed many times by clinical and experimental data. However, there is no consensus among researchers on whether dysbiosis is a cause or consequence of IBD.

IBD is characterized by chronic inflammation of the digestive tract and malfunction of the immune system. Immune cells, including lymphocytes and macrophages, are consistent occupants of the GI track, which is defined as gut-associated lymphoid tissue (GALT). It is comprised of Peyer's patches, lymphoid follicles, and mesenteric lymph nodes. The innate and adaptive immune responses, along with the epithelial barrier, accomplish the enormously difficult task of defending the body against trillions of invaders that populate the lumen of GI track.

There is evidence that genetic aspects of immune responses to pathogenic microorganisms or to harmless components of gut microbiota, partially contribute to the pathogenesis of IBD. Family history is therefore an important risk factor for the onset of IBD. Furthermore, genome-wide association data has identified over 200 IBD loci.

Environment and behavior also factors in IBD

However, only a small population of predisposed individuals will develop IBD, highlighting contributions from other factors, such as changes in the microbiome or environmental factors.  Microbiota profiling in IBD patients indicates a sharp decrease in bacterial diversity with significant changes in the populations of specific strains. These studies showed IBD patients have smaller populations of Lachnospiraceae and Bacteroidetes, but large populations of Proteobacteria and Actinobacteria.

Dysbiosis can also include an imbalance in the virome (total collection of viruses, including bacteriophages, in and on the human body). Clinical findings suggest a significant expansion of certain phages, in particular Caudovirales bacteriophages, in colitis patients. Differences in phage populations and phage species diversity were also found in different types of IBD. In contrast to clinical data, a lower phage diversity was reported in an animal model of colitis.

It is important to highlight that microbiota profiling often uses fecal sample analysis. This approach neglects the importance of subtle, local changes in microbiota as different strains will populate and colonize in the different segment of GI track. Enhanced technologies in gene analysis along with more sensitive sample analysis (biopsy vs. feces) and preservation are also emerging as important tools in the study of dysbiosis and IBD.

Our current understanding of dysbiosis and its contribution to different diseases resembles the blind men and the elephant, where one idea or theory is considered to be absolute. In fact, the opposite is likely. In the last few years, unprecedented progress in our understanding of IBD pathogenesis and factors involved in disease progression has been achieved. These findings strongly suggest that IBD has a multifactorial etiology. Ongoing clinical and preclinical studies with phage and bacteria, either alone or in combination with biologics targeting the immune system, will pave the way to finding the cure for millions of patients suffering from IBD worldwide.

Click on here to reach the first installments of our phage therapy series. And stay tuned for more chapters as we explore how an old treatment is finding new life.