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. 

Bacteria from infants’ microbiome metabolize breast milk differently.

Human milk oligosaccharides (HMOs) are a diverse group of carbohydrates found in breastmilk.  Because the HMOs can’t be used by the infant directly for energy, scientists believe their purpose is to stimulate the development of a healthy gut microbiome.  During the first year of life, an infant’s gut is dominated by Bifidobacteria, in particular B. infantis, and B. bifidum.  In a recent publication scientists measured the difference in HMO utilization between these bugs, and discovered they have very different and important strategies for HMO utilization. The results were published in Nature Scientific Reports.

The scientists first isolated multiple strains of each species, B. infantis and B. bifidum, from the feces of newborn infants.  They then attempted to culture each strain alone in a mixture of HMOs from breastmilk, as well as the individual HMOs alone.  They learned that the each B. infantum strain could grow on pooled HMOs, but interestingly some of the B. bifidum strains could not grow alone on HMOs.  When the bacteria were cultured with mucins (containing sialic acid or fucose, as previously discussed on this blog) none of the B. infantis could grow, whereas most of the B. bifidum could.  This implies that B. infantis alone cannot utilize fucose or sialic acid, but rather needs the help of other bugs to break these down to utilize them.  After, the scientists looked at the regulation of different genes during the culturing experiments.  From these results they determined that B. infantum transports the HMOs inside the cell before breaking them down for energy.  B. bifidum, on the other hand, breaks the oligosaccharides down extracellularly before taking up smaller, simpler sugars. 

All together we see that there is a complex assemblage of bugs in the guts of infants that all rely on one another for energy and metabolism.  The breastmilk cocktail of HMOs itself is so complicated that it almost necessitates the interdependent communities to grow.  Overall, this creates a robust and resilient microbiome that prevents pathogens from taking hold and protects the infant during his or her most vulnerable years.

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.