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. 

New study shows how E. coli and B. theta grow in the gut mucus

The mucosal membrane continues to be one of the most intriguing and vexing components of the gut microbiome.  It is the interface between the body and the environment, it is inhabited many bacteria, and it is a nutritional source that shapes the populations in the gut.  There is still very little known about the specific interactions between gut mucous and bacteria, but this critical system is rapidly being studied.  In the most recent advance, scientists from Switzerland and Germany examined two very different gut bacteria that fill different mucosal niches. They published their results in the journal Nature Communications.  The two bacteria they studied were Bacteroides thetaiotaomicron (B. theta) and Escherichia coli.  B. theta is a slow growing bacteria that has high metabolic flexibility that is capable of directly using gut mucins as an energy source.  E. coli is a fast growing bacteria that is much more limited in its metabolism and can’t directly use the carbohydrates in the gut, but can take hold and rapidly proliferate after a course of antibiotics. 

The researchers meticulously researched gnotobiotic mice and made many discoveries about bacteria in their mucous.  First, they discovered that the mucosal microbiome varies across its thickness, and is sterile closest to the intestines, but rich in life closest to the lumen.  In addition, they noted that the luminal microbiome is distinct from the mucosal microbiome, even though the mucous is constantly being shed into the lumen.  To this end, they confirmed that with regards to E. coli, these bugs replicate faster than they are shed (in about 3 hours in the mucous but 8 hours in the lumen), and that their persistence is due to replication rather than uptake from the lumen.  How though, can E. coli thrive with their limited ability to break down mucins?  The scientists learned that they likely metabolize iron, in addition to atypical carbon sources such as fatty acids and glycerol.  B. theta, on the other hand, has a huge repertoire of genes to break down mucins.  They do, though, have the ability to leave the mucins and form biofilms on bits of food, such as fiber, that pass through the lumen, and this is one way they travel through the gut.  Regardless of whether they are in the lumen or the mucins they proliferate at the same rate.

Each of these bacteria occupy different niches in the gut, and each is important to our health.  The discovery that E. coli can use iron for metabolism is particularly interesting, as chemotrophy is not normally considered as important in the body, and may be important to iron regulation.  As more research is published the mucous appears to be ‘where the rubber meets the road’ in the microbiome, and new discoveries in this area will be crucial to our overall understanding of the microbiome’s interaction with the body.

Ingesting blueberries and oats may modulate the microbiome and help diabetics

Prebiotics are foods that are consumed in order to modulate the microbiome.  They are normally composed of molecules that are not broken down by our body itself, but rather that remain intact until making it to the large intestine where bacteria can break them down.  Common prebiotics come from plant materials, like long chained complex carbohydrates, as well as polyphenols, like blueberry extract.  In a recent study, scientists from Louisiana State University performed randomized dietary intervention on obese subjects and gave them a mixture of these molecules.  They then monitored the changes in the microbiome that occurred, along with changes in health indicators.  Their results were published in The Journal of Diabetes and its Complications.

The researchers included 30 adults in the study, and split them into two groups: one to receive the microbiome modulating dietary supplement, and the other to receive a placebo.  The dietary supplement included blueberry extract, oat bran cellulose, and inulin (a common oligosaccharide of fructose).  The subjects ingested the supplement daily for four weeks, with samples being collected once before and once at the end of the sudy.

Many positive health consequences were associated with eating the prebiotics.  Those patients had improved glucose tolerance, as well as increases in satiety.  The satiety may have been caused by an increase in fasting PYY concentration, a peptide known to cause hunger suppression, which was higher in those people taking the prebiotic.  In addition, there was an increase in self-reported flatulence from taking the prebiotic, but otherwise no adverse events were recorded.  Interestingly, there were no statistically significant changes in the microbiome that resulted from eating the supplement, however higher levels of short chained fatty acids (SCFAs) were observed in the stools of those patients.  Even though no statistically significant change was measured, it is quite possible that the level of sequencing depth and analysis was robust enough to truly observe changes that may have occurred.

This study is another that shows the benefits of eating prebiotics.  Interestingly, the prebiotic used for this study is the same one used by Microbiome Therapeutics in their metformin formulation.  This prebiotic, when combined with metformin, increases its efficacy for diabetics.  This study shows that possibly the prebiotic alone is responsible for this improvement, although it gets us no closer to explaining how this occurs.  Any of our readers that are taking metformin may want to read the wealth of literature around what Microbiome Therapeutics has done, because just the simple addition of foods to the drug seems to improve the results of taking it.

What happens to dietary fiber after we eat it?

Complex carbohydrates from dietary fiber, such as from fruits and vegetables, are, with some exceptions, largely indigestible to normal human metabolism.  These polysaccharides though, form the basis for much of the gut microbiome’s nutrition because they pass into the colon largely unaffected.  For this reason, many scientists are considering complex carbs as prebiotics, or foods that can manipulate the microbiome to improve health.  At this point in time, the fate of many prebiotics in the gut, and the mechanisms by which they are broken down and shared by the microbiome bacteria, are still largely unknown.  Last week a paper in Nature Communications investigated this question, and measured the breakdown of complex xylose molecules in the gut.

The researchers discovered that Bacteroidetes have many different enzymes to break down complex xylans, and regulate and induce different ones based on the type of xylan, e.g. whether or not it has many long chains stemming from its backbone.  They then discovered that these enzymes work in conjunction with one another to break down highly complex structures into smaller oligosaccharides.  These breakdown products are often released into the lumen of the gut where other bacteria can feed on them.  As it turns out, the initial xylan is most important to determining which smaller xylans are produced by Bacteroidetes, and therefore which other bacteria will benefit from the xylan metabolites.  Taken together, this study illustrates the complex ecology of the gut, with some bacteria breaking down large carbohydrates into smaller pieces, and other breaking those down into even smaller pieces, until finally a xylose monosaccharide is broken down into a short chained fatty acid.

Overall, this study lends itself to the value of prebiotics.  Clearly, the food we eat affects the composition of the microbiome.  We are now learning the mechanisms by which this happens, through a hierarchical food chain in the gut.  Once these are completely understood scientists should be able to produce foods that will controllably alter the populations of the gut, which could lead to methods to combat a variety of diseases.

How does the gut microbiome recover after diarrhea?

Scanning electron microscope image of Vibrio cholerae, the cause of cholera and a major cause of diarrhea-associated deaths each year.

Diarrhea is an important global health challenge that kills nearly two million people each year.  Even when it is not lethal it can have important detrimental impacts, especially on children.  For example, frequent diarrhea is associated with decreases in height, IQ, and heart health.  Diarrhea is frequently a microbiome – based disorder, and gut pathogens like enterotoxin producing Escherichia coli and Vibrio cholerae are often the culprits.  Using diarrhea caused by these pathogens as their model, scientists from Harvard University recently studied how the gut microbiome rebounds after diarrhea.  They published their results in Mbio.

The scientists measured the stools of 41 people (both children and adults) in Bangladesh that had diarrhea caused by E. coli or V. cholerae (the cause of cholera).  They measured the patients’ stools before, during, and after their diarrhea episodes and tracked the changes that occurred in all patients’ stools.  Interestingly, they identified a consistent succession of the gut microbiome that occurred in nearly all cases, regardless of the cause of diarrhea.  First, the diarrhea (or antibiotic treatment for the diarrhea) clears out much of the microbiome, and leaves both carbohydrates and oxygen to accumulate in the gut.  (Carbohydrates and oxygen would normally be metabolized by the microbiome, but in the absence of many bacteria, these things accumulate.)  Next, oxygen respiring and carbohydrate utilizing bacteria (especially those using simple carbs) colonize the gut and decrease the abundance of both of these substrates.  After, the lack of simple sugars and oxygen leads to a decline in the population of bacteria that use these, and the succession to anaerobic (i.e. do not respire oxygen), complex carb fermenting bacteria begins.  Finally, the gut microbiome resembles the complex community that existed prior to infection and the onset of diarrhea.  The entire process takes about 30 days to complete, but depends on a variety of factors such as diet, antibiotic use, and duration of diarrhea.

Studies like this one are important to combatting diarrhea, and shortening recovery time.  For example, it is now known that oxygen accumulates after diarrhea, and that while it exists at high levels the microbiome is not fully recovered.  Perhaps introducing an agent after diarrhea that rapidly decreases the amount of oxygen in the terminal gut could hasten the microbiome recovery time and improve the patient’s wellbeing.  Next time you have diarrhea, remember that it takes almost a month for your microbiome to recover, so nurture during that time.