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. 

Red wine and coffee modulate the microbiome

Prebiotics are foods that alter the microbiome.  They are important to many potential microbiome therapeutics because they could be used to shift the microbiome from a dysbiotic, or unhealthy state, to a normal healthy state.  Most scientists that study prebiotics investigate indigestible fiber, because these are known to survive digestion are broken down by specific microbes, thus predictably selecting for specific organisms’ growth.  Recently though, other prebiotics are being studied.  A major class of these are polyphenolic compounds, which provide the antioxidant characteristics of plant material.  Last week researchers from Spain studied the shift in the microbiome that may be induced by red wine and coffee in particular.  They published their results in the journal Food & Function.

The researchers studied 23 patients that had allergic rhinosinusitis or asthma as well as 22 age-matched controls.  They chose individuals with autoimmune diseases because of the promise of prebiotics affecting their diseases.  They asked all of the individuals to fill out a food survey of what they had eaten in the past year, and how often they ate it.  After, the scientists took samples of their feces and measured the bacteria within it.  The scientists found that the abundance of Clostridium, Lactococcus and Lactobacillus was directly associated with polyphenol intake from coffee, and that Bacteroides was positively associated with red wine consumption.  Unfortunately, they noted that these did not differ between allergic people and healthy ones.

This study was certainly lacking in its scope and rigor.  It did not attempt any interventional studies to controllably reproduce these effects, and it did not identifiy specific polyphenols that are responsible.  Nonetheless, it does begin to define how alternative prebiotics may affect our microbiome.  Polyphenols in particular are linked to all sorts of health benefits, normally attributed to their anti-oxidation, however perhaps they positively impact the microbiome as well. 

Fish oil may be important to altering the microbiome, reducing anxiety

Last week we published a blog on the gut-brain axis, and the various associations between brain health and the gut microbiome.  One of the ailments we discussed was depression, which is often studied in mice by inducing early life stress on the mice.  One way to do this is by separating mice from their mothers for hours at a time at a young age.  The Maternal Separation model, as it is known, causes stress and anxiety in these mice, but more importantly, research has shown that it creates a dysbiosis of their gut microbiomes as well.  Many scientists believe the dysbiosis may be implicated in causing some of the stress phenotypes, and so reversing this dysbiosis could have therapeutic value.  Researchers from the University College Cork, in Cork Ireland, experimented with N-3 polyunsaturated fatty acids (PUFAs), like those found in fish oil, in these maternally separated mice, and found they may be important to preventing the dysbiosis.  They published their findings in the journal PLoS ONE.

In the study, the researchers separated mice into two groups, one underwent maternal separation, and the other had a normal upbringing.  Within each group the mice were separated into two more groups, one that received fish oil supplements and the other that didn’t.  Over the course of 17 weeks each groups’ feces were sampled for their microbiomes.  The Maternal separation tended to decrease the bacteroidetes to firmicutes ratio of the mice’s microbiome, which has previously been linked to depression in humans.  Interestingly, supplementation with the fish oil increased this ratio in those maternally separated mice.  In addition, the fish oil also increased the concentration of bacteria that were higher in non-separated mice, such as populations of Rikenella.  Finally, the fish oil increased the amount of butyrate producing bacteria, and as we have seen many times before, butyrate and other short chained fatty acids (SCFAs) are often associated with health.

Overall this study showed that fish oil shifted stressed mice’s microbiome to a more natural state, presumably helping them in the process.  While the scientists did not directly measure stress levels in these mice to support the microbiome connection, hopefully that will be part of a follow up study.  The scientists noted that fish oil is clinically shown to reduce inflammation, and made it a point to connect the stress in the mice to systemic inflammation.  Systemic inflammation is also mediated by the microbiome.  Indeed, people that have inflammation from IBD, for example, do tend to have more stress and anxiety.  In the end, fish oil could make for an interesting prebiotic to shift the microbiome, counteract inflammation, and improve mental health. 

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.