Gut dysbiosis in anorexia nervosa patients

Anorexia nervosa (AN) is a devastating eating disorder in which a patient severely restricts food intake and may have purging behaviors. AN of course results in physical harm but there are also very significant psychosocial effects because of the disease. Studies have shown that the gut microbiome plays an important role in weight gain and it is therefore reasonable to believe that gut dysbiosis could be seen in individuals with anorexia nervosa.

Scientists in Japan characterized the microbiome of AN patients and compared them to healthy controls. They studied 25 women with AN and compared their microbiomes to 21 age-matched healthy females. They found that AN patients had a lower amount of total bacteria and specifically, lower amounts of C. coccoides group, C. leptum subgroup, B. fragilis, and Streptococcus.  

Several papers have shown the importance of gut bacteria on weight gain including those showing the impact that antibiotic use in poultry has on creating larger chickens. Other studies include those linking obesity to specific gut bacteria as well as studies that show transplantation of bacteria, specifically Christensenella minuta, reduced weight gain in mice.

These studies comprehensively show that there is some connection between gut bacteria and weight gain and therefore investigating it as a therapeutic mode for anorexia nervosa is logical. While this study was small in scale and no causal links can be made, it is important to understand that gut bacteria differs between AN patients and healthy controls. Microbiome therapies may be an option for treating anorexia nervosa.

Vacuuming may affect our microbiomes

The westernized lifestyle includes something that we often do not realize is a more important part of our life than it was to people hundreds of years ago: cleaning. With newly developed technology, like vacuuming, we are able to maintain cleaner homes, but this has also increased exposure to allergens such as dust mites. Allergens have a proven impact on the immune system of exposed persons, and as we have seen, the microbiome and the immune system are closely linked. The work of certain Norwegian scientists, published by Microbiome, explores the significance of washing and vacuum cleaning on the gut microbiome of mothers and their children.

The study group included 358 mother-child pairs that were included in a controlled non-randomized longitudinal study called IMPACT (Immunology and Microbiology in Prevention of Allergy among Children in Trondheim). Data was tested for the pregnant woman and then their two-year-old children (two years later). Average cleaning frequencies were 2.9 washings and 6.6 vacuum cleanings per month. For pregnant women, increase in Faecalibacterium prausnitzii showed the strongest association with increased vacuum cleaning frequency in once statistical model, while Roseburia faecis was found to have the strongest association in another statistical model. For the 2-year-old children, the Blautia species in one model, and the Oscillospria species in a second model, were identified as significant.

While the results of this study are a bit confusing, the main point is that the indoor household environment, including hygienic behavior, could have a potentially significant influence on the adult gut microbiome. High frequency of vacuuming could increase allergen presence in the air, which, when breathed in, could go on to influence the immune system – and therefore the microbiome. While many other environmental factors could not be controlled for in this study, the results do bring up the possibility of allergen and microbiota association.       

Drugging the microbiome to decrease atherslcerosis

TMAO is sometimes found in fish.

Trimethylamine N-oxide is a metabolite produced by the microbiome from foods such as red meat and fish.  This metabolite has been independently linked to atherosclerosis, among a host of other diseases.  Researchers at the Cleveland Clinic have been investigating the relationship between the microbiome and this molecule for many years, and we have written about a few of their publications previously.  (Click the TMAO tag below to learn more.)  Most recently, they have researched various compounds that could possibly decrease the production of TMAO by the microbiome.  Last week they published the results of this study in the journal Cell.

The researchers identified a molecule, 3,3-dimethyl-1-butanol (DMB), which inhibited the production of TMAO by gut bacteria.  DMB is a natural product that is commonly found in balsamic vinegar and olive oil.  This molecule was able to shift the microbiome towards bacteria that did not produce TMAO, and importantly, it did not strictly act as an antibiotic and broadly decrease the abundance of microbiome bacteria.  The scientists tested this molecule in mice and showed that it decreased the plasma levels of TMAO in mice that ingested choline.  Moreover, the mice that received DMB had less arterial plaque (i.e. less atherosclerosis).  In addition, the DMB did not appear to have any toxic effects on the mice. 

These researchers hope that the DMB or other agents that lower TMAO levels could possibly be used as therapeutics.   Beyond atherosclerosis, TMAO has been implicated in a number of diseases, ranging from certain cancers to inflammatory diseases.  These diseases are complex though, and their etiologies are not completely understood, so it remains to be seen if this microbiome approach will be successful.  In the mean time, a little less red meat and a little more balsamic vinegar probably won’t hurt.  

Happy and healthy holidays from AMI!

It’s been an incredibly exciting year for AMI and we hope that you have been enjoying our blog posts. We appreciate all the feedback from our readers so if you ever have any thoughts, suggestions, or questions, please reach out to us at blog@microbiomeinstitute.org as we love to hear from you.  We will be off through the New Year to rest up and get ready for another exciting year of microbiome science.

The field of microbiome research grows exponentially every year with new breakthroughs and discoveries coming at an accelerated pace. As new tools are developed and as scientists continue to lay the groundwork for the microbiome field, new microbiome discoveries are going to continue rapidly progressing.  We can’t wait to share with you all the exciting developments of 2016.  

To give you an idea of what the future of microbiome may include, here is a link to a fascinating project being carried out by Jeff Tabor’s group at Rice University profiled by Jennifer Ackerman in Scientific American. His group is working to engineer E. coli to manipulate the microbiome and stave off disease in US naval forces.  

Best wishes for happy holidays and a healthy New Year!

The microbiome affects celiac severity in mice

In non-celiac people, gluten is broken down into its constituent proteins and does not elicit any immune response.  In celiac disease, however, the gluten proteins cause inflammation, which can result in a number of GI issues.  The microbiome has long been thought to play a role in this disease, because of its importance to immune mediation, and its role in gluten breakdown.  An international group of scientists recently tested the role of various different characteristic microbiome communities on the immune reaction in mice with celiac disease.  They published their results last week in the American Journal of Pathology.

The scientists used a mouse model for celiac disease that involved genetically modified mice that had an immune response to gluten.  They split the mice into three groups, one group had a typical healthy microbiome, the next had a healthy microbiome but without proteobacteria, and the final group was germ free (i.e. completely lacking a microbiome).  When the germ free mice were challenged with gluten they had the highest inflammatory response.  This included increases in immune cells, and breakdown of the intestinal villi.  Unsurprisingly, when the germ free mice were colonized with normal microbiota, their inflammatory response was attenuated.   The scientists then discovered an important relationship between celiac’s and Proteobacteria.  The mice that harbored this phylum had more severe responses to gluten, suggesting that these bacteria somehow worsen the inflammatory response to gluten.  Antibiotic treatment that increased the amounts Proteobacteria, and the relative abundances of Escherichia, Helicobacter, Pasteurella, and Lactobacillus, also increased the inflammatory response.

The exact mechanisms by which the microbiome are mediating the immune response are unclear.  Bacteria are known to induce various immune cells and also break down gluten, and these mechanisms may be involved.  In either case gluten sensitivity and celiac disease are clearly affected by the microbiome.

The gut microbiome may contribute to susceptibility to developing alcoholic liver disease

Alcoholic liver disease (ALD) is a major public health issue, yet the underlying mechanisms between ethanol consumption and injury to the liver are poorly understood.  Alcoholics vary in their susceptibility to developing ALD and alcoholic hepatitis (AH) despite consuming similar amounts of alcohol.  Taken together, this evidence suggests that other factors contribute to the onset and progression of ALD other than direct toxicity of alcohol.  Intestinal inflammation and pro-inflammatory bacterial products have also been observed in ALD patients and preclinical mice models, and intestinal dysbiosis has been observed in patients with alcohol dependency.  With this in mind, a team of European researchers devised a strategy to demonstrate microbiome dysbiosis as a casual driver of liver injury. 

The researchers transplanted human gut microbiota into germ-free mice, and the mice were then placed on a high-alcohol diet.  Microbiota were harvested from human alcoholic patients with or without AH (or low severity AH).  Mice transplanted with AH-microbiota had marked increases in symptoms of liver disease as compared to those mice that received microbiota transplants from non-AH alcoholic patients.  These include severe liver inflammation (including increases in T lymphocytes and natural killer cells), more necrosis in the liver, and higher intestinal permeability.  Enterobacteria counts were high in sever-AH patients and faecalibacterium genus was associated with AH-microbiota with low severity.  In an interesting spin, the researchers also transferred microbiota from an alcoholic patient without AH to mice with liver lesions.  Interestingly, mice who had received these microbiota displayed a reduction in serum alanine aminotransferase levels and a decrease in liver regeneration, suggesting that these microbiota could even possibly reverse alcohol-induced liver lesions. 

These findings not only support an association between the gut microbiome and susceptibility to developing alcoholic liver disease, but also provide evidence that these bacteria may drive disease onset.  These were important findings that support microbiota-causal effect rather than dysbiosis as a consequence of liver disease.  This data could perhaps promote development of novel diagnostic techniques that assess the gut microbiome or bacterial metabolites of alcoholic patients.  Methods such as manipulating the microbiome as a therapeutic approach for these patients could also be explored.