Prevotella in the gut appears to improve glucose tolerance

Last week we wrote about a study that showed that the glycemic response from foods was a function of the microbiome, and alluded to the fact that the microbiome likely affects many aspects of metabolism.  Another paper was published this week, in the journal Cell Metabolism, that describes which bacteria are responsible for some of these effects.  The authors describe how Prevotella improve glucose metabolism in healthy human subjects.

The scientists gave 39 subjects white bread and barley bread for three consecutive days and measured their glucose and insulin responses to the diets.  For the most part, the barley bread was associated with an improved response over white bread, but some of the individuals’ responded with a much more stark improvement than others.  The scientists then measured the gut microbiomes of each individual and noted that the microbiome changed in the most responsive individuals, and this change was characterized by an increase in Prevotella (specifically Prevotella copri) and methanogenic archaea.  The opposite effect was seen in the individuals that responded least to the barley bread intervention.  The scientists then confirmed these results in mice.  Mice that were given fecal microbiota transplants from human responders, or P. copri probiotics had improved glycemic responses to high fiber diets than control mice.

Prevotella comes up in a lot of microbiome literature as a bug seen in ‘traditional’ societies that eat a lot of fiber.  This paper demonstrates that many of the genes from Prevotella are crucial to digest the complex fibers and that this may stimulate an improved glycemic response.  Collectively, many papers now support the idea that Prevotella is a critical bacterium to a ‘healthy’ microbiome.

Gut microbiome depletion promotes healthier brown fat and reduces obesity in mice

The white and brown turkey meat from a Thanksgiving dinner

An interesting article from Switzerland was published last week in Nature Medicine.  The scientists reported on a new connection between the gut microbiome and metabolic syndrome (i.e. insulin sensitivity, obesity, etc.)  Whereas most papers observe microbiome disruption and depletion is associated with obesity, this paper describes a different phenomenon: that mice with depleted microbiomes are metabolically healthier than their untouched microbiome counterparts.  As part of the basis for the paper it is important to understand that mammals have two types of fat, brown fat and white fat.  Brown fat is associated with exercise, insulin sensitivity, and health, and white fat is associated with insulin resistance and diabetes.  Brown fat can actually repopulate white fat in a process called browning, and this transition is healthy.  

In the study, the scientists started with either normal mice, germ free mice, or mice that had antibiotics administered to them. They challenged each group of mice with glucose, and noted that antibiotic administration led to improved insulin sensitivity.  When they investigated where the glucose was going, they discovered that it was uptaken by white adipose tissue under the skin.  Then, they compared the normal mice and antibiotic mice, and observed that the antibiotic mice actually had smaller volumes of fat after the glucose uptake.  Interestingly, the fat cells in the germ free and antibiotic mice were smaller and more dense, whereas the normal mice had fewer, larger cells.  The researchers then confirmed that browning of fat was occurring in the germ free and antibiotic mice.  Finally, when the scientists transplanted the microbiome of normal mice into the germ free mice a reversal of many the above described characteristics occurred.  In these mice the fat stopped browning, insulin resistance decreased, and the mice gained weight.

The scientists were able to attribute some of the above phenomena to the release of specific cytokines (molecules that regulate the immune system).  This paper, then, adds to the wealth of research that describes the complex but critical interaction between the gut microbiome, the immune system, and metabolic syndrome.  Although the relationships between these things is yet to be fully understood, this paper may at least change the way you think about the dark and white meat during Thanksgiving dinner this Thursday.

Helminths may increase sensitivity to insulin

Different helminth eggs

Countries that are becoming more exposed to Westernization have experienced many positive health impacts, such as decreases in infectious disease rates.  At the same time, however, there have been some negative consequences, such as increases in type 2 diabetes (T2DM) patients in these developing countries.  T2DM is linked to disruptions in energy balance and increases in systemic inflammation.  Interestingly, helminth infections – i.e., the parasitic worms that can reside in the intestines – have been previously shown to enhance glucose tolerance in animal models as well as induce anti-inflammatory immune responses.  Researchers sought to explore this relationship in humans, hypothesizing that insulin resistance is lower in subjects with soil-transmitted helminth infection. 

A homeostatic model assessment for insulin resistance (HOMAIR) test was used to examine insulin resistance in 646 adult study participants on Flores Island in Indonesia.  Soil-transmitted helminth (STH) infection is common on this island.  The HOMAIR model measures insulin in blood samples in a well-validated insulin-resistance assay.  Stool samples were also collected from the subjects, and microscopy and PCR were used to detect various helminth species. 

Of the 646 participants, 424 were STH-infected while 222 were not.  In the STH-infected cohort, participants were further categorized by how many different species were found.  Body mass index and waist to hip ratio were significantly lower in the STH-infected group, suggesting STH-infection may be beneficial toward glucose metabolism.  Furthermore, there was an association between the number of distinct STH species present and HOMAIR.  For every additional species found in a subject, there was an incremental decrease in homeostatic insulin resistance. 

These experiments display an interesting causal relationship between STH species and insulin resistance, however there were certainly limitations.  No association was found between subjects in systemic inflammation in infected versus non-infected groups, failing to elucidate modulations of inflammatory pathways that could be correlated with the observed trends.  Additionally, the changes in insulin resistance may be related to a change in body-mass index rather than helminth infection.  Specifically, participants located in more rural areas may have more active, healthier lifestyles, and would be subsequently leaner and thus more sensitive to insulin.  On top of this, patients with helminths tend to exhibit lower weight in general as these parasites significantly affect metabolism. 

Despite these limitations, this study points to an interesting relationship that is deserving of more examination.  This epidemiology research will impact global health policy and can offer good perspective as more nations around the world are on the path toward development.