Butyrate in human milk negatively associated with infant weight and BMI

Human milk (HM) contains butyrate, a short-chain fatty acid (SCFA). This four-carbon fatty acid is present in HM at a varied concentration of 0.1–0.75 mg/100 mL. Butyrate has many biological functions, such as anti-inflammatory properties, and prevents insulin resistance and obesity. A recent study in the journal Nutrients provided evidence on the origin of HM butyrate based on HM microbiota composition. This study also elucidated the maternal and antenatal factors linked with HM butyrate concentration.

Study: Butyrate in Human Milk: Associations with Milk Microbiota, Milk Intake Volume, and Infant Growth. Image Credit: evso / Shutterstock

Background

Previous studies have revealed that gut anaerobic bacteria synthesize butyrate via fermentation of non-digestible carbohydrates. Among many SCFAs (e.g., acetate and propionate), butyrate is a significant energy source used by colonic epithelial cells. 

Although much research related to intestinal butyrate is available, not many studies have elucidated the origins of HM butyrate. It has been hypothesized that maternal gut microbiota synthesizes butyrate, which might reach HM through maternal circulation. To date, no evidence has been documented that indicates local butyrate production through in situ HM microbiota. In addition, it is imperative to understand whether maternal and pregnancy-related factors influence HM butyrate concentration.

Infants are introduced to this fatty acid through oral intake of HM or solid food. Another way through which infants receive butyrate is bacterial fermentation of dietary compounds, particularly human milk oligosaccharides (HMOs), in the colon. Hence, HM butyrate does not represent the actual butyrate concentration consumed by infants. The benefits of HM butyrate for infants have been indicated in many studies. For instance, HM butyrate prevents unnecessary weight and adiposity gain, which substantially decreases later obesity risk. Therefore, it is important to measure the absolute butyrate intake via HM to better understand the mechanistic links with weight and adiposity gains.

About the Study

This current longitudinal prospective cohort is part of the Cambridge Baby Growth and Breastfeeding Study which aims to elucidate the factors in HM that influence infants’ growth rate and identify parameters that enhance the risk of obesity in later life. The authors measured the total HM consumed by a baby using a deuterium-labeled water technique. The HM composition, i.e., its macronutrients, butyrate, HMOs, HM microbiota, and infant’s gut microbiome, was also evaluated.

In this study, mother-infant pairs were recruited at birth at the Rosie Maternity Hospital in England. Healthy mothers with healthy body mass index (BMI) before pregnancy and who had the intention of breastfeeding up to at least six weeks of the infants’ age were included in this study.

Birth weights were obtained at different time points, i.e., at birth, 2 and 6 weeks, and then 3, 6, and 12 months. A Holtain Tanner/Whitehouse Skinfold Caliper was used to measure relative subcutaneous body fat and skinfold thickness (SFT). HM samples were collected to determine composition.

Study Findings

A total of 71 healthy singletons were included in this longitudinal study to analyze how HM butyrate influences infant growth. Overall, negative associations were found between HM butyrate concentrations and measures of infant weight and adiposity. This finding was in line with a previous study that reported butyrate to prevent excessive weight gain and obesity during childhood.

Since HM butyrate concentration was found to be inversely correlated with HM intake volume, it was presumed that high butyrate concentration in HM could be the reason for low HM intake in some infants. The authors speculated that butyrate odor and/or taste in HM and its ability to regulate appetite can potentially decrease infant HM intake. This might also cause early attenuation from HM intake, resulting in early infant weight gain.

Notably, the current study reported a relative abundance of Oscillospira in HM, a common butyrate producer. However, other butyrate producers, such as Faecalibacterium prausnitzii, Roseburia intestinalis, or Eubacterium rectale, were not detected. The authors did not expect the presence of butyrate-producing bacteria of the gut microbial community, typically anaerobes, in HM. Therefore, increased bacterial metabolism could be attributed to the increased HM butyrate levels and not to changes in bacterial community composition.

Interestingly, a positive correlation between butyrate concentrations and non-butyrate-producing bacterial taxa in HM (e.g., Acinetobacter sp.) was observed. The abundance of Acinetobacter in HM microbiota was associated with food allergy in infants. In addition, butyrate exhibited an antimonial effect on certain strains of Acinetobacter; therefore, the abundance of this species was not associated with butyrate synthesis.

Conclusions

HM butyrate was found to be negatively associated with infants’ growth. However, this association was found to weaken with age, potentially because of the baby’s introduction to other forms of nutrition. Notably, a weak relationship between HM butyrate and HM microbiota composition was observed in this study.