gut microbiome

Microbiome affects blood glucose levels after eating, can help predict glycemic response to foods

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Postprandial (post-meal) glycemic response (PPGR) is the effect that food has on blood glucose levels.   Eating a sugary candy, for example, will raise blood glucose levels, whereas drinking water will not.  PPGR remains an important predictor for metabolic syndrome and type II diabetes, so it has an important role the obesity epidemic.  Unfortunately, PPGR is difficult to predict, and efforts that are based on individual foods themselves have failed.  New research shows that there are many factors, including the microbiome, that are important to predicting blood glucose after a meal.  The research out of Israel and published in the journal Cell presents a new model that can more accurately predict PPGR that is based on personalized factors.

The researchers catalogued 800 peoples’ meals over 7 days while continuously measuring their blood glucose levels.  In addition they monitored their gut microbiota, weight, sleep, and various other lifestyle factors.  After evaluating the data, the scientists realized that identical foods had vastly different PPGRs.  For example, bread could have a 8 fold variation in glycemic response depending on the individual.  In order to explain these differences, the scientists identified several significant associations between the microbiome and the PPGR from specific foods.  For example, on the phyla level high abundances of Proteobacteria and Enterobacteriaceae were associated with poor glycemic controls.  On the species level Eubacterium rectale, which is known to ferment fiber, was correlated with low glycemic response, and Parabacteroides distasonis, which had previously been associated with obesity, was correlated with hight glycemic response.  The scientists then aggregated all of their data, including microbiome data, and created a predictive algorithm for the PPGR from foods for individuals.  This algorithm accurately predicted the glycemic response from foods on a personalized level, and was more informative than general food based predictions.

This study speaks to the power of personalized medicine that is based on the microbiome.  Knowledge of our own microbiome could be used to advise our dietary choices in order to choose foods that will lead to low PPGR, and decrease our risk for metabolic syndrome.  Overall, the scientists determined that of all foods, eating fiber was most beneficial because it lowers glycemic response over the long term.

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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.

Antibiotics affect the mouth and gut differently

When we discuss antibiotic resistance, it’s not always clear where the resistance is developing or how exactly the resistance develops. A study out of the UK and Sweden looked at two niches, the gut and the mouth, to understand the difference between how the different parts of the body react to antibiotics.

The scientists discovered that these two parts of the body reacted and recovered very differently after a one-week course of antibiotics. They took fecal and saliva samples prior to the antibiotic regime and then gave the study participants a weeklong course of clindamycin, ciprofloxacin, minocycline, amoxicillin, or a placebo and continued taking fecal and saliva samples for a year.

They found that the oral microbiome recovered much faster than the gut microbiome back to its normal state. It took much longer for the gut microbiome to recover and for participants taking ciprofloxacin, diversity was changed even after 12 months. They also found that while participants largely had genes associated with antibiotic resistance in their gut prior to the trial, the amount of antibiotic resistant genes increased after taking the antibiotic. Antibiotic resistant genes in the mouth remained largely stable before and after treatment.  It was also observed that butyrate production, a health associated short-chain fatty acid, was severely affected by ciprofloxacin and clindamycin.

This raises a number of questions like why does the oral microbiome recover so much faster than the gut microbiome? And why isn’t there a similar increase in antibiotic resistant genes in the mouth like we see in the gut? While this study raises many questions, it provides an opportunity to look at the mouth and better understand what is unique about that environment in comparison to the gut. 

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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.

Prebiotics in human breast milk are associated with infant weight

Human breast milk contains nutrients and compounds that are beneficial for infants. Human milk oligosaccharides (HMOs) are a group of important complex carbohydrates that are found in breast milk. These HMOs are important in the developing infant because they serve as a prebiotic, helping to shape the infant’s gut microbiome by facilitating the selection of beneficial bacteria. The link between gut microbiota composition and infant obesity has led to speculation that HMOs might affect certain bacteria that in turn lead to decreased body fat. Because HMO composition of female breast milk varies over the course of lactation, researchers in Oklahoma and California tested to see whether differences in milk HMO content are associated with infant body weight. The results of their study were published in The American Journal of Clinical Nutrition.

Twenty-five mother-infant pairs participated in this study. On average, the mothers were 29.5 years of age and overweight before conception. When the infants were 1 month and 6 months old, the mothers supplied breast milk samples to test for HMO composition. Concurrently, the infants’ body fat composition, weight, and length were measured.

The findings suggest that HMOs are associated with infant body weight, fat mass, and lean mass at both 1 month and 6 months. A diversity of HMOs, such as LNFFPI (lacto-N-fucopentaose I, a sugar), DSLNT (difucosyl-LNT, a sugar), and FDSLNH (fucosyl-disialyl-lacto-N-hexaose, a sugar) accounted for 33% of the fat mass, which was more than other variables such as gender, and mothers’ pregnancy BMI. infant fat mass than did sex, pregnancy BMI.  LNFPI was inversely associated with 1 month old infant weight, while at 6 months it was inversely associated with weight, lean mass, and fat mass. Overall, the presence of a diverse group of HMOs decreased infant body mass.  While this study has its limitations because it does not specifically test the bacterial composition of the gut, it is a first step to identifying an association between HMOs and infant BMI. As obesity remains an epidemic in the United States, perhaps the microbiome is the first place to look towards to prevent the disease. 

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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.

There are important differences in the gut mucus of germ free and conventionally raised mice

Mucus is not just produced by snails.

Mucus is not just produced by snails.

The mucus lining of our intestines are the critical interface between the microbiome and the epithelial cells that make up the intestines.  It provides many essential roles in its interaction with the microbiome, but perhaps most importantly it is a physical barrier that separates microbiome bacteria from the vasculature.  Without it, bacteria can elicit an immune response which results in inflammation that is characteristic of IBDs.  New research out of Sweden shows how mucus changes over time as the result of microbiome colonization.  The results were published in the journal Cell Host and Microbe last week.

The researchers undertook a number of experiments whereby they measured the mucus in germ free and conventionally raised mice.  In general, the conventionally raised mice had thinner, more easily shed mucus in their small intestines that allow for diffusion of nutrients.  This mucus contained antimicrobial peptides that prevented bacteria from passing across it.  The conventional mice’s large intestines’ mucus was thick and stiff and impenetrable to bacteria.  This mucus maintained most of its properties even after the conventionally raised mic were treated with antibiotics.  On the other hand, the germ free mice had thin and stiff mucus in their small intestines, as well as thick, but easily penetrable mucus in their large intestines.  This shows that the conditions under which the mucus develops is important to its eventual structure and function.  After, the scientists inoculated some of the germ free mice with the microbiome of the conventional mice and monitored the mucus over time.  It took an entire 6 weeks for the mucus to finally resemble the mucus of a conventionally raised mice.  In addition, the scientists looked that the glycans that were being formed in the mucus, and also noticed differences between the germ free and conventional mice.  As discussed on this blog previously, these glycans can be important in determining which bacteria colonize the gut.  To that end, the researchers measured the microbiome in the mice and discovered that conventional mice had a higher Firmicutes to Bacteroidetes ratio compared to germ free mice.  In addition, even after the germ free mice had been inoculated with the new bacteria, their microbiomes never truly matched the conventionally raised mice’s.

More than anything, this paper shows us the critical importance that mucus plays in microbiome health, science and research.  It demonstrates the importance of an early life microbiome to the maturation of a healthy mucus that can properly regulate the microbiome.  It also shows a possible negative consequence of antibiotics or dietary compounds can have on the mucus, and by extension the microbiome.  Finally, among many other things, it shows that microbiome research should consider the effect of the mucus on their experiments, especially ones involving germ free mice. 

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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.

Helminths suppress the immune system by modulating the gut microbiota

The nematode  Heligmosomoides polygyrus , which was used in this study, seen into an optical microscope. Taken from the digestive tractus of a rodent.

The nematode Heligmosomoides polygyrus, which was used in this study, seen into an optical microscope. Taken from the digestive tractus of a rodent.

Helminths, or gut worms, are known to be powerful suppressants of the immune system.  In fact, this is the basis for using helminth therapy for various autoimmune conditions, such as IBD.  Still though, the mechanisms for helminth immunosuppression is unknown.  There have been some studies that suggest the worms are secreting molecules that have this anti-inflammatory effect, but this may not tell the whole story.  Researchers from Switzerland hypothesized that because helminths and our gut bacteria evolved together, it was likely that the helminths were modulating the bacterial gut microbiome, and that this modulation was anti-inflammatory.  They tested and published results that support this idea in the latest issue of Cell Immunity.

The scientists started by showing the efficacy of a mouse helminth, Heligmosomoides polygyrus bakeri (Hpb), in reducing inflammation in mouse models of asthma.  The scientists infected mice with the parasite and exposed those mice, along with non-infected control mice, to dust mites in order to elicit and immune response.  The scientists observed that the Hpb mice had much lower circulating levels of specific cytokines and immune cells after exposure to dust mites than the controls.  Next, the scientist gave the Hpb infected mice antibiotics, which eliminated the gut bacteria but left the helminths intact.  They then exposed these mice and control mice to dust mites to elicit the immune response.  Interestingly, while the helminths alone did decrease the levels of some inflammatory molecules and cells, inflammation still occurred, similar to what was observed in controls.  This meant that the gut bacteria play a role in modulating the helminthic immune suppression.  In order to validate these findings, the scientists then performed fecal microbiota transplants from control mice or helminth infected mice into germ free mice (with no worms).  After, the challenged these mice with house dust mites and discovered that the gut bacteria alone created an immune suppression in the mice, even in the absence of the worms.

The researchers attempted to identify which bacteria may be causing this immune suppression, and measured the microbiomes of the mice.  They noted that higher levels of Clostridiales occurred in the Hpb mice.  They then measured the levels of short chain fatty acids (SCFAs) in the mice’s guts, because Clostridiales are known to produce SCFAs.  They noticed that higher levels of SCFAs, which have previously been linked to immune suppression, did occur in higher levels in mice with Hpb compared to controls.  The scientists then studied this connection between worm infection and increase in SCFAs in pigs and humans.  Remarkably, the increase in SCFAs in helminth-infected subjects compared to controls was observed across species, suggesting the immune suppressing helminth phenomenon is extensible to many mammals.  The researchers even investigated possible mechanisms for why SCFAs were able to suppress the immune system.  They discovered the SCFAs were binding specific receptors that modulate T-cells, and more depth on this issue can be found by reading the paper. 

This study is quite important as it shows that helminths in combination with the bacterial microbiome are important to immune suppression.  This suggests that future therapeutics that may take advantage of helminth-derived molecules may not be as effective.  It does, however, support helminth therapy as an immune suppressant.  However, helminths are also very dangerous and can lead to various diseases.   So, while clinical trials that use helminths are underway, there are still no approved uses for worms.  

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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 microbiome’s response to the flu and its treatment

In 2013 there was an avian flu (H7N9) outbreak in China that affected 140 people, killing 46 of them.  During the outbreak doctors from one of the major hospitals in China treated 40 of these patients by giving them antivirals and antibiotics, amongst other first line treatments.  In addition, they gave probiotics along with the antibiotics to restore the gut microbiome.  All the while, they measured the patients’ microbiomes to track how they changed throughout the course of treatment.  The results of this study were published last week in the journal Nature Scientific Reports.

Twenty six patients were enrolled in the study, and each of them was given antibiotics within 6 hours of admission to the hospital.  In addition, each one was given Clostridia probiotic capsules along with the antibiotics.  Thirty one healthy control stool samples that represented the demographics of those undergoing flu treatment were also measured as a part of the study.  Before the antibiotics were taken, the patients with the flu already had altered microbiomes that were low in diversity and had lower abundances of Bacteroidetes and higher levels of Proteobacteria.  After antibiotics were given there was a dramatic shift in the microbiomes, that was characterized by a relative increase in the abundance of Escherichia coli.  In addition, the scientists noted that the probiotics were in fact increasing the amounts of Clostridia in the guts of patients who took them, and that the probiotics may have led to better clinical outcomes.  In their hospital only 20% of patients died of the flu, whereas 40% died in the rest of China.

The major takeaway from this study is the changes that the flu has on the microbiome, decreasing diversity and altering the levels of certain phyla.  The fact that the probiotics did appear to take hold and improve clinical outcomes is interesting, but the study was extremely small and limited in its scope to reach any statistically significant conclusions.  Overall though, this study suggests that if you come down with a flu that it may be wise to feed and nourish your microbiome because it is ‘getting sick’ right alongside you.

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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.