Algorithms that can analyze the microbiome after diet induced changes

An increasing body of evidence supports that the gut microbiome composition can alter host metabolism, and eventually result in disease.  To date most of these studies have pointed to associations between the microbiota and host metabolism, but little has been able to demonstrate causal relationships between the two.  To address this, researchers from Sweden developed a specialized computational platform called CASINO (Community and System-level Interactive Optimization) to quantify the release and consumption of metabolites from gut microbiota, and pairing this data to dietary intake characteristics and patterns.  CASINO in a multidimensional platform, but ties both species richness/diversity to dietary intake in the gut microbiome.  The algorithms were optimized to distinguish bacteria that consumed carbohydrates/metabolites, and those that produce metabolites instead. 

In an in vitro validation test, the CASINO simulation was able to predict net production of metabolites produced by each community and was even able to distinguish between the syntheses of more essential amino acids as compared to non-essential amino acids.  In the past, researchers have been able to link two to three species to metabolic consumption rates.  Using CASINO, researchers in this study were able to write algorithms that could analyze at least five species.  The analysis quantified the contribution of individual bacteria to the overall microbiome, as it was shown that B. thetaiotaomicron, E. rectale, and F. prausnitzii dominated metabolism. 

CASINO was also used in a clinical experiment.  Data was examined from an experiment in which 45 overweight and obese individuals were given a restricted low-calorie diet for 6 weeks.  The simulation was able to characterize species diversity and composition.  After characterizing the species, CASINO was also used to simulate the effect of diet on the gut microbiome composition at baseline and after diet intervention in the test subjects.  CASINO algorithms were able to predict a decrease in carbohydrate consumption and increase in amino acid consumption (i.e. protein) by analysis of microbiota metabolites of the five select gut bacterial species. 

The CASINO algorithms examined most metabolic functions and allowed several species to be included in a simulation.  Furthermore, the authors propose that the program is scalable to include more than five species.  CASINO could pave the way toward development of quantification methods that could serve as a predictive interaction tool, especially in light of the importance of biomarkers in predicting disease onset.  We discussed biomarkers last week in our blog regarding renal disease, and these types of tools could provide exceptional value for clinical diagnostics.

Study finds that C-sections are not a risk factor for IBD

Inflammatory bowel disease (IBD) is a disease of the gut made up primarily of two diseases, primarily Crohn's disease and ulcerative colitis. In IBD, the gut and other parts of the digestive tract are attacked by the body's own immune system.  It is not clear how or why IBD occurs but there is a significant amount of research looking at this. It is known that the human gut microbiome goes through a lot of changes from birth through the first few years of life before stabilizing into the “adult” composition. Therefore, looking at the first years of life could be critical for understanding IBD. Researchers in Canada, in a study published by Clinical Gastroenterology and Hepatology, set out to determine if birth by Cesarean section increases likelihood of IBD.

The logic behind this hypothesis is that birth by vaginal delivery would expose the infant to the mother’s vaginal bacteria, which could possibly be essential in the development of the infant’s own microbiome. To study whether C-sections are a risk factor for IBD, the researchers gathered data from the University of Manitoba IBD Epidemiology Database, which keeps health records of all Manitobans diagnosed with IBD between 1984 and March 2010. These records were matched with birth and maternal health records. 1,671 IBD patients were linkable with mothers and therefore used for analysis. 10,488 matched controls were also used.

Analysis showed that IBD patients were no more likely to be born by C-section than the controls. Additionally, urban rather than rural residence was associated with higher instances of IBD. Within families, the likelihood of IBD was not different between C-section and non-C-section siblings.  

In conclusion, there does not appear to be an increased risk for inflammatory bowel disease if a child is born by C-section. Factors such as breastfeeding, socioeconomics, living environment, pets, etc. are still being analyzed for possible contribution to gut microbiome dysbiosis.

New contraceptive vaginal ring does not increase risk of vaginal infections

The Nuvaring, a type of vaginal ring.

A newly developed contraceptive device that consists of a vaginal ring that is meant to be used for an entire year is currently under development.  As part of this device’s safety trials the scientists who developed the device monitored how it would impact the vaginal microbiome.  The vaginal microbiome is critical to vaginal health, and certain changes to the vaginal flora are associated with bacterial vaginosis (BV), yeast infections, and other vaginal diseases.  Implanting devices will certainly affect the vaginal microbiome, but fortunately, the scientists determined that the device did not increase the likelihood of getting a vaginal microbiome-mediated disease.  They published their results last week in PLoS ONE.

The vaginal microbiomes of 120 women using the device were measured over the course of a year.  There were no significant increase in the rates of BV over the course of the year.  In addition, the levels of Lactobacilli, which are associated with a healthy vagina, and Gardnerella vaginalis, which has been associated with BV, remained relatively unchanged over the course of treatment.  In addition, measurements on the actual surface of the vaginal ring matched the overall vagina quite well in terms of microbial colonization. In both cases, Lactobacilli dominated.

Any fluid or device inserted into the vagina should be considered for its effect on the vaginal microbiome, for example, douching is associated with BV.  Fortunately, this safety study showed that the vaginal ring did not increase rates of disease, so women out there using a vaginal ring for contraception need not be too concerned that their ring is negatively impacting their vaginal health.

Periodontitis and its possible contribution to preterm birth

Evidence is accumulating that gum disease can lead to chronic systemic inflammation throughout the entire body.  In fact, bacteria from the mouth may be entering the vasculature through the gums and can wind up in various places around the body, like in the plaques that cause heart attacks.  Another location that these mouth bacteria can end up is in the placenta of expecting mothers.  This is important because of the increasing association between the placental microbiome and preterm birth.  Researchers from Spain investigated this connection by determining the placental microbiomes of pregnant women with and without periodontitis.  The results of their study were published last week in the journal Oral Diseases.

The researchers measured the placental microbiomes of 57 pregnant women, as well as determined their periodontitis statuses.  They discovered that the abundance of placental bacteria was significantly higher in women with periodontitis.  In addition, they identified Fusobacterium nucleatum was significantly higher in the placentas of women with periodontitis.  Also, 90% of women who had either preterm birth or very low birth weight infants carried F. nucleatum, compared to 62% of full term pregnancies.

Interestingly, other studies have shown F. nucleatum in the mouths of folks with deep gum pockets, which strengthens this connection between the conditions.  It is strange to consider the relationship between the mouth and placenta, which have seemingly little in common.  However, the microbiome of both are connected by the vasculature, and they apparently share many of the same bugs.  Until further research can establish better connections between these pregnancy outcomes and the microbiome we recommend all expecting mothers to floss and brush their teeth every day.

Gut-microbiota metabolites could be associated with renal failure

It’s becoming increasingly recognized that dysbiosis in the gut microbiome can result in the development of sickness or disease.  Understanding these implications, researchers have also turned to studying biomarkers and indicators that can better predict this outcome and disease onset.  A novel and easily detectable biomarker could serve as an indicator of dysbiosis and facilitate therapeutic development.   Renal function decline is a disorder that can eventually lead to chronic kidney disease (CKD )and impacts many people worldwide.  A conglomerate team of researchers investigated whether metabolites produced from bacterial fermentation could serve as early indicators of renal function decline, and whether or not disruption to taxonomic units are detectible in this stage of the disease. 

The researchers measured circulating metabolites in 4439 individual healthy patients with minimal renal function decline.  Estimated glomerular filtration rate (eGFR) was measured as an indicator for reduced renal function, and the onset of CKD was defined by the kidney losing half of its filtration capacity.  It was found that indoxyl-sulfate, p-cresyl-sulfate, and phenylacetylglutamine –metabolic products of gut microbiota fermentation of tyrosine and tryptophan – were associated with reduction in eGFR, suggesting that these markers could be indicators of early renal function decline.  The researchers were also able to correlate these metabolite levels with changes to in intestinal flora.  16S sequencing revealed that 3 operational taxonomic units were correlated with indoxyl-sulfate, 52 with phenylacetylglutamine, and 1 with p-cresyl sulfate. 

Specific changes within the gut microbiome could indicate disease onset, and these changes could perhaps be monitored by circulating metabolic products.  Following metabolic activity could allow clinicians to treat disease early in its progression, and this principle could theoretically apply to a variety of host diseases, not just kidney failure.  Metabolic products of the microbiome could serve as a useful tool that can lead to novel therapy development.  

Dietary fiber promotes microbiome richness and stability

The richness and stability of gut bacteria play an important role in microbiome homeostasis. We’ve chronicled many ways to perturb or alter the microbiome but diet is an area that has long been studied as a way to modify the microbiome.  Specifically, dietary fiber has been shown to alter the microbiome and a recent study out of France looked at the microbiome of individuals who were given high fiber diets compared to normal diets.

19 people participated in a nutritional study and ate a normal diet for five days supplemented with 10 or 40 grams of dietary fiber per day. After the short-term intervention, there was a 15 day washout period and fecal samples were analyzed using qPCR and 16s RNA sequencing at various stages of the experiment. 

The scientists found that the increase in dietary fiber intake did have an effect on the microbiota populations however it was dependent on the richness which varied from individual to individual. They also found that for the individuals on the 10 g fiber per day diet, microboime changes were not associated with richness and therefore it may be possible that other factors are playing a role in microbiome dynamics. Higher microbiome stability was seen with increased richness as well as a higher Prevotella:Bacteroides ratio.

This study showed that microbiome richness is a key factor that needs to be analyzed when comparing individuals’ responses to dietary interventions. Microbiome richness should be studied as we look at other factors such as antibiotic intake, aging, among others. This study also proposes that subjects with low microbiome richness should undergo long-term interventions such as diets with high vegetable diversity to try and improve overall microbiome richness.