Mouse guts can harbor a variety of microbiomes

The microbiome of a zebrafish (shown above) was successfully transplanted into a mouse gut.

An article was recently published in Cell that explored how bacteria from various microbiomes colonize in a mouse gut environment.  Researchers, including Jeffrey Gordon, introduced microbiota from different habitats to groups of mice. These habitats included human, termite, and zebrafish gut microbes, microbes from human skin and tongue, and communities from soil and marine sediment.

Results suggested that the mouse gut, while selective, provides an environment in which all of the above microbiomes can survive. Results also showed that when cohousing a mouse with an already established normal microbiome alongside a mouse that had a foreign microbiome, the foreign microbiome is not able to colonize in the mouse with indigenous microbiota.

In another experiment, researchers cohoused three mice: one harboring mouse gut microbiota, one with human gut microbiota, and one that was raised in a sterile germ-free environment. Results showed that in the first few days the human gut microbiota colonized the sterile mouse before the normal mouse microbiota was able to, however, after 2 weeks’ time the normal mouse microbiome took hold in all three mice. This suggests that while it is possible for opportunistic microbiomes to establish themselves, the mouse microbiome will eventually fulfill its ecological niche, as it is best suited for the mouse gut environment.

This study helps lay the foundation for future probiotic research because it describes the ability of mice to host a variety of foreign microbiomes, and the necessary conditions to do so.

Probiotics and diet affect mouse offspring gender and survival

An article published in late September by researchers at the Massachusetts Institute of Technology in the Journal of Probiotics and Health shows the importance of the maternal microbiome in the gender and survival of their offspring. Eight-week-old female mice were fed a control diet, a diet representing human fast food consumption, or a diet in which their drinking water was supplemented by the probiotic Lactobacillus reuteri, a bacterium that has been implicated in female oxytocin regulation. Another group of oxytocin-deficient female mice were fed a control diet, or a control diet supplemented by the probiotic. The mice were mated and offspring were observed for three generations.

The researchers concluded that offspring survival increased when mice were given L. reuteri in their diets, and survival decreased significantly with the consumption of a ‘fast food’ diet when compared to the control group. They also concluded that probiotic-treated wild type mothers had an increase in number of female offspring.  However, no increase in female progeny was observed in the probiotic treated mice that were oxytocin deficient, suggesting that probiotic exposure affects levels of oxytocin in females, and this leads to the increase in female offspring.

This research is significant in that it links probiotic intake of mothers to survival of offspring and sex of offspring. It also shows a possible relationship between the microbiome and the hormone oxytocin, which is linked to reproductive and social behavior in female mammals.

Current challenges in microbiome research

Scanning electron micrograph of E. Coli bacterium.

Curtis Huttenhower, Rob Knight, Owen White, Jacques Ravel (all members of our SAB), and others recently published a commentary titled "Advancing the Microbiome Research Community" in Cell.  The paper was a 'State of the Microbiome' address and outlined the current challenges and the future outlooks of the microbiome field.

Among the many challenges they outlined include how to design causality studies, and how to attribute causality of phenotypes to specific bacteria, proteins, or metabolites.  The paper also discussed the bioinformatics bottleneck that is occurring in the field, as the necessary expertise required to properly analyze sequencing data is severely lacking.  There also lacks a proper centralized online repository for all sequencing data that is generated.  This sequencing data needs to include metadata that would describe how the data was generated.  Furthermore, the authors describe the need for guidance on how to properly define and comprehensively describe phenotypes, such as inflammatory bowel disease (IBD), in microbiome studies.  Without this standardization, proper comparison between studies can not take place.  Finally, institutional review boards (IRBs) need guidance on how to properly regulate human microbiome studies in order for scientists to properly prepare and carry out their projects.

While the above areas are only a few of the challenges facing the field, each of them reinforces the mission and programs of the AMI.  The MBQC is standardizing techniques and creating rigorously tested analytical protocols by investigating the sources of variation in microbiome testing.  In addition, the AMI is focusing on future data repository efforts.  These are just a few of the areas we hope to serve the field in the coming years.  We believe a nonprofit, specifically the AMI, can help fill these voids and address many of the issues outlined in this paper.

A new microbiome pill to treat C. diff

A paper recently published in the Journal of the American Medical Association shows the results of using a microbiome pill in treating C. diff infections.  In the article, the researchers from Massachusetts General Hospital created oral pills containing fecal samples.  Fecal material was first acquired from donors and then screened using common blood screening techniques.  The pills were created by blending the fecal samples with saline then straining the liquid and adding it to pills before freezing for preservation.  

20 patients suffering from C. diff were then given 15 pills on two consecutive days.  14 of 20 patients recovered from their symptoms after just 1 treatment with the pills.  In the other 6 cases, 5 recovered after a second treatment 8 weeks later.  Only 1 of the 20 patients was not symptom free after 2 treatments and none of the patients suffered from any recognized side effects.  It should be noted that the study did not have a control group treated with placebos.

This study has important implications on traditional fecal microbiota transplants (FMTs).  Currently, the rectal introduction of FMTs has implicit dangers, especially if not performed by a medical professional.  An oral pill FMT is less invasive, and allows for easier storage and administration.

Exercise and the microbiome

A few months ago an article was published in the journal Gut that investigated the connection between the microbiome and exercise.  In the study, 40 elite rugby players and 46 healthy men who were not professional athletes with similar body mass indexes from Ireland were studied.  Stool and blood samples were taken from each person, as well as a survey on their exercise and eating habits.

The scientists discovered that:

1) Blood samples showed that athletes had lower inflammatory markers relative to the non-athletes.
2) Athletes had a higher diversity of gut microbiota than non-athletes.
3) Several specific taxa were abundant in the athletes' guts, including Akkermansia, which has been implicated in gut health in mice.
4) Exercise and consumption of protein was associated with greater gut microbiome diversity.

This is a very interesting study, and one of the first that makes a connection between exercise and biodiversity.

Alcoholism and the microbiome

An article was recently published in PNAS that investigated the relationship between alcohol dependence and the microbiome.  The authors had previously shown that alcohol-dependent people are at higher risk for a 'leaky gut', in which some molecules, such as bacterial metabolites, are passing through the GI tract into the bloodstream.  Leaky guts cause an inflammatory response that leads to further health issues.  In their new study, the authors investigated whether alcohol craving, and depression are associated with the gut microbiome, and suggest the possibility of targeting the microbiome as a therapeutic modality during alcoholism recovery.

The authors studied 60 alcohol dependent subjects who recently stopped drinking and measured their microbiome, leakiness of gut, and mood.  They immediately discovered that the leakiness of the gut was associated with alcohol craving during withdrawal.  The more leaky the gut, the more the subject craved alcohol, whereas patients with less leaky guts had less psychological addictions.

The authors also discovered that leakier guts were associated with microbiome dysbiosis, which included many bacteria associated with inflammatory bowel disease (IBD).  Other studies have shown that similar dysbioses are associated with leaky guts in IBD patients, and in recovering alcoholics the dysbiosis can last long after cessation of drinking.  

This study suggests that potential treatments for recovering alcoholics could include targeting the microbiome to bring it back to a more 'normal' state.  This normal state will decrease the permeability of the gut (make it less leaky), and thus decrease the psychological addiction to alcohol.