secondary bile acids

Americans swap foods with Africans and their microbiomes follow – fiber, fat and cancer risk

Phuto pap and porridge, a traditional South African, high fiber, meal.

Phuto pap and porridge, a traditional South African, high fiber, meal.

Despite having similar genetic backgrounds, African Americans are thirteen times more likely to develop colon cancer than rural South Africans.  Indeed, environmental factors, rather than genetics, are thought to be the major factor in developing colon cancer, because recent immigrants’ children’s risk is more similar to where they are living than to their parents’ homeland.  This environmental risk could be primarily caused by a number of factors, such as antibiotic use or drug use, but many scientists believe that diet, and its influence on the microbiome, is primarily responsible.  As it turns out, rural Africans eat much more fiber (almost 5x more) and much less fat (almost 3x less) than African Americans, and these differences have drastic effects on the microbiomes of their hosts.  Not only are the most abundant bacterial species different, but the major metabolites vary greatly as well.  Scientists from the University of Pittsburgh came up with the clever idea of swapping the foods of rural South Africans and African Americans, to investigate how this dietary intervention would affect each group’s microbiomes and risk for colon cancer.  They published the results of their study in Nature Communications last week.

The researchers studied 20 middle aged African American men and 20 middle aged rural South African men.  They each had their microbiomes and colons studied for two weeks while eating their normal diets, and then again for two weeks after swapping diets.  Initially, the Americans had microbiomes dominated by Bacteroides and the Africans by Prevotella.  After the diet though, they noticed a rapid shift in these populations, and it corresponded to an increase in colonic inflammation for the Africans and decrease in the Americans.  In addition, an increase in butyrate, the short chained fatty acid (SCFA) that is thought to be beneficial to health, followed the fiber diet as well, and a decrease was associated with eating the high fat diet; this makes sense, as butyrate is produced as a metabolite of fiber fermentation by the microbiome.  Interestingly, prior to the diet change a top-level analysis of all the metabolic end products of the microbiome showed that Africans produced more of every single one studied except for choline, which is related to heart disease.  Many of the metabolites studied, including choline, followed their diet switch, and were produced according to the food eaten, rather than the person eating it.  Perhaps most importantly, secondary bile acids, which are produced by the microbiome and may be carcinogenic and an important cause of colon cancer, followed the diet as well.  Africans, who produced much fewer secondary bile acids than Americans while consuming their regular diet, had a 400% increase in production after the diet switch, and vice versa for the Americans, who had a 70% decrease.

This study really illustrates the importance of diet on the output of the microbiome.  These metabolites can directly influence our health, and may be more important to our well-being than the bacteria that produce them.  According to this study, it appears that eating more veggies and less fat, something that parents have been saying for a long time, fits in with our understanding of the microbiome.  As Erica Sonnenburg said in our podcast 3 weeks ago, “Feed your microbiome at every meal!”

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

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.

New research on the timeline and mechanisms of C. diff infections

Protein structure of  C. diff  toxin B

Protein structure of C. diff toxin B

Clostridia difficile infections are often the subject of this blog, but we rarely ever discuss how the infection actually occurs.  Scientists know that C. diff spores, which are not very uncommon in nature, can enter the gut from a variety of sources.  Once the spores reach the gut they normally just pass through unnoticed.  However, given the right conditions, these spores can take hold, germinate, and grow.  At some point during infection, the C. diff produces toxins which can compromise gut permeability (i.e. cause ‘leaky gut’) which leads to inflammation and all the nasty effects associated with the disease.  The exact gut conditions that trigger C. diff spore germination are not known, but scientists are convinced that the microbiome is involved because taking antibiotics, which wipe out the normal gut flora, make people susceptible to C. diff infection.  Some research has suggested that certain bugs in the microbiome outcompete C. diff for resources.  Other research shows that secondary bile acids, which are produced when the microbiome breaks down bile acids, inhibit C. diff germination.  Scientists are still working hard to understand the mechanisms of this infection, and just this week research out of the University of Michigan, published in Infection and Immunity, has shed new light on the process. 

The scientists first gave a group of mice antibiotics to make them susceptible to infection, and then fed the mice C. diff spores.  After, they euthanized mice every 6 hours to measure the progression of C. diff infection.  They learned that within 6 hours the spores had already germinated and entered the vegetative state in the feces and large intestine of the mice.  Over time, the C. diff progressed their way up the distal end of the large intestine all the way to the stomach, until the entire gastrointestinal (GI) tract was infected.  After 30 hours, sporulation of C. diff occurred, and interestingly this coincided with the production of C. diff toxins.  These toxins were found throughout the GI tract, however, inflammation only occurred in the large intestine, and not in the small intestine.  After 36 hours the infection had become severe enough that all animals were euthanized.

The scientists also measured the bacterial population and bile acid content of the gut during the infection.  After antibiotic treatment the microbiome was drastically altered and Lactobacillaceae flourished.  Once infection took hold the Lactobacillaceae were supplanted by C. diff in the large intestine, although the Lactobacillaceae still dominated the small intestine population, which, notably, did not become inflamed.  Secondary bile acids, which are produced by the microbiome and linked to C. diff germination, were abundant prior to antibiotics.  After antibiotic treatment, the large intestine had fewer secondary bile acids, and in the most infected regions had no detectable secondary bile acids.

This research is the first to develop a timeline for C. diff infection in mice, and strikingly it occurs very rapidly, with symptoms showing within 2 days.  This study also supports the notion that an altered microbiome is critical to C. diff infection, and that secondary bile acids may in fact play a crucial role in keeping C. diff from vegetating.  Interestingly, this study fits in well with a previous study we wrote about that showed the benefits of secondary bile acids in preventing C. diff infection.

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

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.