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      Human Milk Short-Chain Fatty Acid Composition is Associated with Adiposity Outcomes in Infants

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          ABSTRACT

          Background

          Presumed benefits of human milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient composition. However, data on breast milk composition and its relation with growth are sparse.

          Objective

          We investigated whether short-chain fatty acids (SCFAs), known to be present in HM and linked to energy metabolism, are associated with infancy anthropometrics.

          Methods

          In a prospective birth cohort, HM hindmilk samples were collected from 619 lactating mothers at 4–8 wk postnatally [median (IQR) age: 33.9 (31.3–36.5) y, body mass index (BMI) (kg/m2): 22.8 (20.9–25.2)]. Their offspring, born at 40.1 (39.1–41.0) wk gestation with weight 3.56 (3.22–3.87) kg and 51% male, were assessed with measurement of weight, length, and skinfold thickness at ages 3, 12, and 24 mo, and transformed to age- and sex-adjusted z scores. HM SCFAs were measured by 1H-nuclear magnetic resonance spectroscopy (NMR) and GC-MS. Multivariable linear regression models were conducted to analyze the relations between NMR HM SCFAs and infancy growth parameters with adjustment for potential confounders.

          Results

          NMR peaks for HM butyrate, acetate, and formic acid, but not propionate, were detected. Butyrate peaks were 17.8% higher in HM from exclusively breastfeeding mothers than mixed-feeding mothers (P = 0.003). HM butyrate peak values were negatively associated with changes in infant weight (standardized B  = −0.10, P = 0.019) and BMI (B = −0.10, P = 0.018) between 3 and 12 mo, and negatively associated with BMI (B = −0.10, P = 0.018) and mean skinfold thickness (B = −0.10, P = 0.049) at age 12 mo. HM formic acid peak values showed a consistent negative association with infant BMI at all time points (B < = −0.10, P < = 0.014), whereas HM acetate was negatively associated with skinfold thickness at 3 mo (B = −0.10, P = 0.028) and 24 mo (B = −0.10, P = 0.036).

          Conclusions

          These results suggest that HM SCFAs play a beneficial role in weight gain and adiposity during infancy. Further knowledge of HM SCFA function may inform future strategies to support healthy growth.

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          Most cited references18

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          Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?

          High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.
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            Towards microbial fermentation metabolites as markers for health benefits of prebiotics

            Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.
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              The SCFA Receptor GPR43 and Energy Metabolism

              Free fatty acids (FFAs) are essential nutrients and act as signaling molecules in various cellular processes via binding with FFA receptors. Of these receptors, GPR43 is activated by short-chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate). During feeding, SCFAs are produced by microbial fermentation of dietary fiber in the gut, and these SCFAs become important energy sources for the host. The gut microbiota affects nutrient acquisition and energy regulation of the host and can influence the development of obesity, insulin resistance, and diabetes. Recently, GPR43 has been reported to regulate host energy homeostasis in the gastrointestinal tract and adipose tissues. Hence, GPR43 is also thought to be a potential drug target for metabolic disorders, such as obesity and diabetes. In this review, we summarize the identification, structure, and activities of GPR43, with a focus on host energy regulation, and present an essential overview of our current understanding of its physiological roles in host energy regulation that is mediated by gut microbiota. We also discuss the potential for GPR43 as a therapeutic target.
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                Author and article information

                Journal
                The Journal of Nutrition
                Oxford University Press (OUP)
                0022-3166
                1541-6100
                May 2019
                May 01 2019
                May 03 2019
                May 2019
                May 01 2019
                May 03 2019
                : 149
                : 5
                : 716-722
                Affiliations
                [1 ]Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
                [2 ]Mead Johnson Pediatric Nutrition Institute, Nijmegen, the Netherlands
                [3 ]Department of Agrotechnology and Food Sciences, Wageningen University, the Netherlands
                [4 ]MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom
                [5 ]Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom
                Article
                10.1093/jn/nxy320
                31050748
                a610eb7a-3b20-45f2-a578-6e4378e5d9ea
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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