Is there any association between gut microbiota and type 1 diabetes?

Recently "gut microbiota" has become a trendy area of research for many different diseases, including type-1 diabetes.  Gut microbiota refers to the microorganisms which grow inside a person's digestive tract.  Over the last few years there have been some papers published showing changes in the gut microbiota at the time of T1D diagnosis, or differences between the gut microbiota between people who get T1D and those that don't.  However, because gut microbiota has only recently been studied, it is hard to tell if these differences mean anything or if they are normal variations.  Even if they do mean something, it is also not clear if they are a cause of T1D or a symptom of T1D.

Recently a group in Tehran systematically searched for all English language scientific papers that dealt with gut microbiota and T1D and reviewed the 26 papers that they found.  You can read their paper here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791003

The papers they reviewed covered about 2600 people in 17 different countries.  The top line results were that 24 out of 26 papers found some changes or differences in the gut microbiota between people with T1D and those without.

However, I wanted to see if these 24 studies found the same differences between people with T1D or different differences.  For example, if one study found that people with T1D had more of bacteria A, while another study found they had more of bacteria B, and a third found they had less of bacteria C, well those all found "differences" but it is not at all clear that these matter.  On the other hand if the three studies all found more of bacteria A, then (in my opinion) that is a much stronger finding.

My Data Analysis

I started out with the list of results that the researchers provided in their "table 3".  This was a list of each study, and each microbe that the study found to be either increased or decreased between the people who had T1D and who did not.  (Since we are looking for differences, either an increase or a decrease might be important.)

With that list, I then scored each microbe family, giving it +1 for every study which found an increase and a -1 for each study that found a decrease in levels when comparing people with T1D to those without.  I then looked for microbe families which had a score of +4 or greater, or those that had a -4 or smaller.  These would be microbe families which showed a difference in several different studies.

There are two limitations with my data analysis technique:

1. I did my analysis on a study by study basis, which means that a larger study carries the same weight as a smaller study.  Obviously, that is not ideal, but it does make the analysis easier.
2. Some of the studies tested for specific species (such as "Bifidobacterium adolescentis") while other studies only tested for families (such as "Bifidobacterium spp." with "spp." standing for "any species").  Unfortunately, if one study found Bifidobacterium adolescentis but another found Bifidobacterium spp. there is no way to know if they both found the same species or not.  Therefore, I did my analysis at the family level.  So I would say that both studies found a Bifidobacterium spp.

My Results

The only family of microbes which had a strong signal was Bacteroides spp.  Ten different studies found increase levels of these microbes in people with T1D, and only one study found decreased levels.  That is a net score of +9.

The Blautia spp. had a net score of +4, with 4 studies showing an increase and none showing a decrease.

I was surprised by the number of bacteria families were different in only 1 or 2 out of 24 studies.   For me, this implies that either there is a lot of natural variation in gut microbiota, or that we are not good at measuring it, or that we are not measuring the right parts of it.  In any case, it suggests that we should not depend too much on these studies.  If something really was different, we would expect to see it in more than 1 or 2 studies.

I was even more surprised by the number of bacteria families that were found increased in some studies, but decreased in other studies.  There were over 10 of these.  That is even more worrisome, because it suggests the results might just be random variation.  And with a little bad luck, maybe the Bacteroides spp. and Blautia spp. might be random variation as well. (Normally, p values are used to estimate the chance of random variations being mistaken for real results.  However, because this is a summary of many different sized studies, I don't think p value analysis is a reasonable thing to do here.)

My Opinion

Overall, having gone through this exercise, I'm less likely to think the gut microbiota is important to type-1 diabetes.  The more I look at these studies, the more I think we don't have enough history and background studying the gut microbiota to understand the differences that we are seeing, and even be sure they are "real" differences.  However, if there are differences, then we should look for them in the Bacteroides and Blautia families first.  Those are the most likely places to see differences.

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com 

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.