Research shows that the microbiome can control certain phenotypes

Structure of immunoglobulin A

Structure of immunoglobulin A

Immunoglobulin A (IgA) is an antibody that is produced in the mucosal linings and is thought to play a critical role in maintaining the homeostasis between the body and the microbiome.  IgA deficiency has been related to celiac disease and people who suffer from this deficiency are prone to bacterial infections.  While studying IgA in mice, folks from Washington University, St. Louis noticed that IgA was not found in the feces of some mice, but was found in high levels in others.  They investigated this high/low fecal IgA phenotype and showed that it was directly related to the microbiome.  Their results were published last week in Nature.

The researchers began by doing various experiments between the high and low IgA mice.  They first noted that mothers would pass their IgA phenotype to all their offspring, showing the trait was vertically transmitted.  They then put high and low IgA mice in the same cages and learned that the low IgA trait was dominant, and high IgA mice would rapidly become low IgA mice.  In order to discover if a virus was responsible, the scientists filtered the feces of low IgA mice to remove any bacteria and then transferred it into high IgA mice.  These mice remained high in IgA, meaning that a bacteria, fungi, or other larger organisms were likely responsible. 

The scientists then began experimentation with antibiotics.  When broad spectrum antibiotics were given to low IgA mice it eliminated most of the bacteria in their gut.  When these mice were given fecal transplants from high IgA mice, they became high IgA mice.   This trait was also transferred to their progeny, and their children became high IgA mice.  In addition, when the antibiotic ampicillin was administered to low IgA mice, their feces became high in IgA.  Overall, these experiments led the scientists to believe that bacteria were responsible for the secreted IgA levels, and that ampicillin had the ability to kill whichever bacteria caused the low IgA phenotype. 

The scientists then performed genetic analysis on all of their mice's stools to see which bacteria were present in high and low IgA fecal samples.  There was one bacterial genus, Suterella, which was common to only low IgA mice.  When this bacteria was cultured and given to high IgA mice, it caused them to become low IgA mice.  Suterella apparently has the ability to confer the low IgA phenotype. (Interestingly, we had previously written about Suterella and its link to Down Syndrome and autism.)

Finally, the scientists studied the mechanism that could prevent IgA from being secreted in the low IgA mice, and they learned that it is likely the microbiome is both degrading IgA itself, and that it is degrading the proteins in the mucous responsible for secreting IgA.

Taken together these results show a very robust link between a specific phenotype and the microbiome.  Before this study, most relationships between phenotypes, such as obesity, and the microbiome were merely associations, rather than causative.  This study though, is crucial in that it shows secreted IgA levels can be directly caused by the microbiome, and there is a mechanism that explains the phenomenon.  

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

The role of the gut microbiome in Down Syndrome

Down Syndrome is the most common genetic cause of intellectual disability and occurs when there is an extra 21st chromosome, trisomy 21. Down Syndrome patients often experience premature aging and are therefore at early risk for age-related conditions like Alzheimer’s disease. Scientists from Italy published a study in November in PLOS One that compared the gut microbiome of Down Syndrome patients with that of healthy individuals.

The scientists hypothesized that the gut microbiome of Down Syndrome (DS) patients was contributing to the aging of the patients and would present similarly to the microbiome of an aged individual. They compared the gut microbiome of 17 patients with DS with previously published data for 16 age-matched individuals as well as 5 elderly individuals and 3 individuals who were 100 years old.  Interestingly, they found that the microbiomes of patients with DS were very similar to the microbiomes of healthy individuals. In this case, their hypothesis did not end up as they predicted. 

It is important to note that this study only included 17 test subjects who were all under the age of 35.  Future studies will need to be conducted with larger patient cohorts as well as older patients to truly get a good understanding of the gut microbiome profiles of the entire population of patients and better understand this hypothesis. 

There was, however, an unexpected finding that I found to be quite interesting. While the general makeup of the DS patients' microbiomes were similar to those of healthy individuals, there were subpopulations of bacteria that were more or less abundant in DS patients. Individuals with DS had elevated levels of Parasporobacterium and Sutterella and reduced levels of Veilonellaceae. This increase of Sutterella and decrease of Veilonellaceae has previously been described in autistic children with stomach problems. Specifically in this study, Sutterella abundance was positively correlated with Aberrant Behavior Checklist (ABC) scores for the DS individuals. The ABC test is a 58 item report checklist used to assess maladaptive behavior in people with developmental disabilities. 

This positive correlation tells us that this bacterium in the gut may play a role in maladaptive behavior in patients with various conditions. Although the original hypothesis was not confirmed, this very interesting result will need to be further explored to better understand the role of the gut microbiome in individuals with autism spectrum disorder and Down Syndrome.


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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.