A Very Thorough Overview of Autoimmunity and Gut Microbiome Research

Little girl with a mouseOver the past two decades, researchers have been focusing heavily on the relationship between our intestinal contents and various diseases, trying to determine if there is a causal association.  Many had suspected for years prior to this that the two were somehow related, but without the evidence needed to support such suspicions.  Now the increased interest in this investigative area is starting to produce real and potentially useful information regarding these connections.  Here we examine the possibility of links between autoimmune disease and the diverse collection of organisms with which we share our bodies, with particular focus on our “gut”, or intestinal tract.

What is the gut microbiome?

The “gut microbiome” is the microscopic communal environment within our lower intestines that includes a diversity of microorganisms (the “gut flora”), most of which are various forms of bacteria.  While we often think of microbes like bacteria as harmful to the body, these intestinal bugs are a normal and essential component of our digestive and immune systems.  The microbes that exist within our colons perform a host of specific functions necessary for individual metabolic tasks, and in more general terms, contribute greatly to our overall health by maintaining or disturbing a well-balanced microscopic community.

When this balance is upset, a variety of pathologies may result; and since a large percentage of our immune system resides within the gut, these often include autoimmune illnesses.  The alteration of the gut flora may produce changes in immune function by stimulating or inhibiting localized immune factors, which then often promote functional changes in other areas of the body.

An example that some readers may be familiar with is colonization of the colon with C. difficile (an opportunistic bacteria related to the organism that causes botulism) after extensive antibiotic administration in susceptible individuals.  In short, the antibiotics that help clear one infection successfully also inadvertently clear too many beneficial bacteria from the intestines, allowing the C. diff to grow unchecked (usually controlled by the missing bacteria).  When this happens, the patient must then deal with a secondary intestinal infection that often requires extended doses of specific antimicrobials.  This is but one way in which a normal or disrupted gut microbiome can affect the health and well being of its host.

What studies are going on that link gut microbiome findings to autoimmune disease (onset, progression, symptoms)?

Since the 1990s, interest in this area of research has exploded.  Although the work, in terms of scientific study, is still very much in its infancy, it has produced some truly amazing findings that have caused a radical shift in our thinking on autoimmune and other diseases.  There have been a range of findings implicating the makeup of our gut flora in the promotion of or protection against autoimmune illness, all of which have helped to shed light on the exact processes taking place.

Many different disorders have been examined with respect to this connection, but the four most studied autoimmune diseases appear to be rheumatoid arthritis (RA), inflammatory bowel disease (IBD; Crohn’s and ulcerative colitis), diabetes mellitus and multiple sclerosis (MS).  All of these research efforts have endeavored to find the nature of the associations between the particular disorders and the normal/abnormal gut microbiome.  They have produced a number of fascinating findings already, and much work continues to be performed in pursuit of this goal.

Recently, studies have yielded an enhanced understanding of various pathologies and/or the causative mechanisms that initiate them.  With regard to RA (one of the most extensively studied diseases in this respect), in 2010 investigators discovered that patients, either newly diagnosed or untreated, had significantly higher populations of specific bacteria in the gut and mouth when compared with controls.

And they found that certain beneficial species were lower than normal in these same subjects.  Additionally, they noted that certain bugs incited production of immune components known to play some role in autoimmune pathogenesis of different conditions.  More recent findings have helped support these initial discoveries, such as this article from Mayo Clinic and updates released in late 2013 from NYU researchers.  There are also some good in-depth articles from 2011 from Rheumatologist.org and Nature.

One particularly interesting study showed that the introduction of a single type of bacteria in the sterile gut of mice was enough to induce an immune-mediated arthritis.

Another disorder that has received a lot of attention recently is type 1 diabetes, known to be an autoimmune disease that destroys the islet cells of the pancreas.   A series of investigations and reviews have shown a clear association in mice between the composition and alteration of gut flora and the development of type 1 diabetes.

In addition to this generalized finding, researchers also found, unexpectedly, an impact of gut flora on sex hormones, which may have implications in explaining why females are more often affected by autoimmune disease than their male counterparts.  Briefly, they noticed that female mice with a high predisposition for diabetes became highly protected from the disease when receiving a fecal transplant from male mice; and even more surprisingly, this change in gut microbiome appeared to also raise the levels of testosterone in the females, suggesting that sex hormone differentiation is at work on some level.

Furthermore, the gut microbiome has even been linked to type 2 diabetes, which is not considered an autoimmune disease; patients with the disorder had distinctly different gut populations from those without.

Other medical and psychiatric conditions have been examined for connections to the gut microbiome as well.  IBD and MS are two such disorders that have attracted the attention of researchers.  This has included the proposition that pregnancy-related changes in the gut microbiome may partly explain why pregnant women with IBD often improve during the gestational period.

Interestingly, the research on MS seems to indicate that it is normal flora – rather than disease-causing organisms – that, when combined with a genetic predisposition, can lead to the development of the disease.  Altered intestinal flora have also been implicated as possible factors in other autoimmune neurologic and neuropsychiatric diseases, including such conditions as depression, OCD and schizophrenia.

What applications to prevention and treatment of autoimmune disease might come from this research?

One of the most important applications of this information will come in the form of a better understanding of how our diet affects our gut microbiome, and thus how it affects the various diseases associated with normal and changed intestinal environments.  Because our diet has changed so drastically over the past century, an improved conception of how this has transformed our immune status will be invaluable in educating people on the best and worst food items in terms of autoimmune illnesses.  The future will likely see doctors and nutritionists recommending certain foods while discouraging consumption of others, based on disease predispositions and population studies.  How far off such counseling may be is still uncertain.

A related area of interest that will probably play an increasingly important role in both prevention and treatment of autoimmune disease is that of probiotics.  Probiotics are the group of naturally occurring or extrinsic microbial species that help perform essential intestinal functions.  Additive supplements contain different mixtures of beneficial bacteria, meant to either promote normal healthy gut function and/or treat gastrointestinal disorders arising from an imbalance of gut flora.  Probiotics have demonstrated importance and efficacy in controlling a host of immune responses, and have recently shown some promise in the treatment of type 1 diabetes.

Once our understanding of this seemingly crucial connection between the gut microbiome and autoimmune illness is further elucidated, it will undoubtedly have implications for diagnosis of disease.  It is reasonable to assume that when this knowledge is sufficiently expanded, we will benefit from the development of diagnostic tests derived from an increased comprehension of the role of the microbiome in disease states.  The obvious benefit in early diagnosis is the ability to begin treatment sooner, and hopefully halt progression of the disorder in question and improve signs and symptoms of disease.

Towards this end, research such as that described above will continue to yield treatment advances.  Just as some patients have experienced success using currently available probiotic remedies, therapies designed to specifically alter certain aspects of the gut flora will no doubt play a large role in the treatment of autoimmune conditions.  Finding out how to tweak this microbial environment for our benefit will help to reduce inflammation and promote normal functioning.  Some such advances have already been seen in IBD patients who have received fecal transplants from normal donors, at which point their symptoms significantly decline.

In light of all this information, there are also a few things that patients can do to help control the integrity of the gut microbiome and prevent unnecessary illness.   First, it is important to not take antibiotics when they are not needed.  Even most bacterial illnesses will resolve on their own, but when antibiotics are required, one should take them exactly as directed and only for the amount of time required to treat the infection.   As mentioned above with regard to C. diff infection, antibiotics, while immensely helpful in some situations, also have a negative impact on healthy bacteria in the gut, especially when used for long periods of time.  Unfortunately, there are doctors out there who prescribe extended antibiotic regimens for diseases that don’t exist or don’t require such treatment.  Be wary of such prescriptions, and in the case of any doubt regarding this therapy, please get a second opinion.

Similarly, unless you are directed to do so by a competent physician, DO NOT receive colonics or perform similar cleanses that can potentially disrupt this delicate microbial community.  Despite the fact that such “therapies” may feel good, they are generally not good for you, and are not recommended, for reasons that should be clear by now.  They may feel pleasant at the time or immediately afterward, but these procedures have at best little to no effect on your health.  In the worst case scenario, undergoing such ill-advised treatments can alter your gut flora substantially, leading to any number of illnesses or complications, including nasty intestinal infections that are then more difficult to eradicate.  As always, when in doubt or considering new treatment avenues, always err on the side of caution by consulting your healthcare provider.

Questions for your doctor:

  • Can you recommend a good source of information regarding the connection between autoimmunity and gut microbiome?
  • Are there certain foods that I should either avoid completely or be sure to consume, with regards to protecting the gut flora?
  • Based on my specific condition(s), which probiotic supplements might be helpful for my symptoms and disease progression?
  • Are there any clinical trials that might be appropriate for me to participate in?
  • Is there any place for colonics or other similar treatments in treating my disease or in promoting general health?  Do they actually “detox” the system?  What are the risks?

About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians.  After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time.  He may be reached at [email protected].

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Comments

  1. These are good notes. I wrote about foods that probably cause autoimmune disease at http://jesusdiedandlives.wordpress.com . Great job!

  2. Great info! Agreed it’s very important to keep your gut healthy to manage autoimmune diseases. Check out our line of vitamins and probiotics. http://www.normalhealthy.com

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