Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4 Months: Differences in Relative versus Absolute Concentrations

Sarah L Bridgman, Meghan B Azad, Catherine J Field, Andrea M Haqq, Allan B Becker, Piushkumar J Mandhane, Padmaja Subbarao, Stuart E Turvey, Malcolm R Sears, James A Scott, David S Wishart, Anita L Kozyrskyj, CHILD Study Investigators, M R Sears, P Subbarao, S S Anand, M Azad, A B Becker, A D Befus, M Brauer, J R Brook, E Chen, M Cyr, D Daley, S Dell, J A Denburg, Q Duan, T Eiwegger, H Grasemann, K HayGlass, R Hegele, D L Holness, P Hystad, M S Kobor, T R Kollman, A L Kozyrskyj, C Laprise, W Y W Lou, J Macri, P J Mandhane, G Miller, T Moraes, P D Paré, C Ramsey, F Ratjen, A Sandford, J A Scott, J Scott, F Silverman, E Simons, T Takaro, S Tebbutt, T To, S E Turvey, Sarah L Bridgman, Meghan B Azad, Catherine J Field, Andrea M Haqq, Allan B Becker, Piushkumar J Mandhane, Padmaja Subbarao, Stuart E Turvey, Malcolm R Sears, James A Scott, David S Wishart, Anita L Kozyrskyj, CHILD Study Investigators, M R Sears, P Subbarao, S S Anand, M Azad, A B Becker, A D Befus, M Brauer, J R Brook, E Chen, M Cyr, D Daley, S Dell, J A Denburg, Q Duan, T Eiwegger, H Grasemann, K HayGlass, R Hegele, D L Holness, P Hystad, M S Kobor, T R Kollman, A L Kozyrskyj, C Laprise, W Y W Lou, J Macri, P J Mandhane, G Miller, T Moraes, P D Paré, C Ramsey, F Ratjen, A Sandford, J A Scott, J Scott, F Silverman, E Simons, T Takaro, S Tebbutt, T To, S E Turvey

Abstract

Our gut microbiota provide a number of important functions, one of which is the metabolism of dietary fiber and other macronutrients that are undigested by the host. The main products of this fermentation process are short-chain fatty acids (SCFAs) and other intermediate metabolites including lactate and succinate. Production of these metabolites is dependent on diet and gut microbiota composition. There is increasing evidence for the role of SCFAs in host physiology and metabolic processes as well as chronic inflammatory conditions such as allergic disease and obesity. We aimed to investigate differences in fecal SCFAs and intermediate metabolites in 163 infants at 3-5 months of age according to breastfeeding status. Compared to no exposure to human milk at time of fecal sample collection, exclusive breastfeeding was associated with lower absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the relative proportion of acetate was higher with exclusive breastfeeding. Compared to non-breastfed infants, those exclusively breastfed were four times more likely (aOR 4.50, 95% CI 1.58-12.82) to have a higher proportion of acetate relative to other SCFAs in their gut. This association was independent of birth mode, intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or socioeconomic status. Our study confirms that breastfeeding strongly influences the composition of fecal microbial metabolites in infancy.

Keywords: breastfeeding; gut microbiota; infants; lactate; short-chain fatty acids; succinate.

Figures

Figure 1
Figure 1
Mean relative proportion of short-chain fatty acid according to breastfeeding status. N = 158. Breastfeeding status at fecal sample collection.
Figure 2
Figure 2
Acetate fecal concentration (A) and as a relative proportion of total short-chain fatty acid (B), according to breastfeeding status at fecal sample collection. N = 158. Comparisons by non-parametric Kruskal–Wallis test (with Bonferroni posttest for multiple comparison). Box plots present the group median (thick black line), upper quartile (top of box), and lower quartile (bottom of box). Whiskers present the maximum and minimum values excluding outliers (denoted by circles).
Figure 3
Figure 3
Effect of infant diet on fecal short-chain fatty acids (SCFAs) and potential effect on host metabolic and immune programming. Human milk feeding causes changes in infant fecal metabolites, potentially through effects on gut microbiota composition (a). Changes in concentrations and relative proportions of SCFA and intermediate metabolites exert local effects on the gut environment and act as signaling molecules effecting host metabolism and immune system. These actions may have important programming effects on inflammatory-mediated diseases in childhood, including obesity and allergic disease (b).

References

    1. Victora CG, Bahl R, Barros AJ, Franca GV, Horton S, Krasevec J, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet (2016) 387:475–90.10.1016/S0140-6736(15)01024-7
    1. Sommer F, Backhed F. The gut microbiota – masters of host development and physiology. Nat Rev Microbiol (2013) 11:227–38.10.1038/nrmicro2974
    1. Kumari M, Kozyrskyj AL. Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation. Obes Rev (2017) 18:18–31.10.1111/obr.12484
    1. Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol (2016) 1:1.10.1111/1462-2920.13589
    1. Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev (1990) 70:567–90.
    1. Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell (2016) 165:1332–45.10.1016/j.cell.2016.05.041
    1. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes (2016) 7:189–200.10.1080/19490976.2015.1134082
    1. Correa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol (2016) 5:e73.10.1038/cti.2016.17
    1. Richards JL, Yap YA, McLeod KH, Mackay CR, Marino E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunol (2016) 5:e82.10.1038/cti.2016.29
    1. Flint HJ, Duncan SH, Scott KP, Louis P. Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc (2015) 74:13–22.10.1017/S0029665114001463
    1. Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG (2016) 123:983–93.10.1111/1471-0528.13601
    1. Martin R, Makino H, Yavuz AC, Ben-Amor K, Roelofs M, Ishikawa E, et al. Early-life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS One (2016) 11:e0158498.10.1371/journal.pone.0158498
    1. Yassour M, Vatanen T, Siljander H, Hamalainen AM, Harkonen T, Ryhanen SJ, et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med (2016) 8:343ra81.10.1126/scitranslmed.aad0917
    1. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev (2015) 91:619–22.10.1016/j.earlhumdev.2015.09.001
    1. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ (2013) 185:385–94.10.1503/cmaj.121189
    1. Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe (2015) 17:690–703.10.1016/j.chom.2015.04.004
    1. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics (2006) 118:511–21.10.1542/peds.2005-2824
    1. Chow J, Panasevich MR, Alexander D, Vester Boler BM, Rossoni Serao MC, Faber TA, et al. Fecal metabolomics of healthy breast-fed versus formula-fed infants before and during in vitro batch culture fermentation. J Proteome Res (2014) 13:2534–42.10.1021/pr500011w
    1. Edwards CA, Parrett AM, Balmer SE, Wharton BA. Faecal short chain fatty acids in breast-fed and formula-fed babies. Acta Paediatr (1994) 83:459–62.10.1111/j.1651-2227.1994.tb13059.x
    1. Martin FP, Moco S, Montoliu I, Collino S, Da Silva L, Rezzi S, et al. Impact of breast-feeding and high- and low-protein formula on the metabolism and growth of infants from overweight and obese mothers. Pediatr Res (2014) 75:535–43.10.1038/pr.2013.250
    1. Midtvedt AC, Midtvedt T. Production of short chain fatty acids by the intestinal microflora during the first 2 years of human life. J Pediatr Gastroenterol Nutr (1992) 15:395–403.10.1097/00005176-199211000-00005
    1. Ogawa K, Ben RA, Pons S, de Paolo MI, Bustos Fernandez L. Volatile fatty acids, lactic acid, and pH in the stools of breast-fed and bottle-fed infants. J Pediatr Gastroenterol Nutr (1992) 15:248–52.10.1097/00005176-199210000-00004
    1. Siigur U, Ormisson A, Tamm A. Faecal short-chain fatty acids in breast-fed and bottle-fed infants. Acta Paediatr (1993) 82:536–8.10.1111/j.1651-2227.1993.tb12747.x
    1. Pham VT, Lacroix C, Braegger CP, Chassard C. Early colonization of functional groups of microbes in the infant gut. Environ Microbiol (2016) 18:2246–58.10.1111/1462-2920.13316
    1. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, et al. The Canadian Healthy Infant Longitudinal Development (CHILD) study: examining developmental origins of allergy and asthma. Thorax (2015) 70:998–1000.10.1136/thoraxjnl-2015-207246
    1. Matysik S, Le Roy CI, Liebisch G, Claus SP. Metabolomics of fecal samples: a practical consideration. Trends Food Sci Technol (2016) 57:244–55.10.1016/j.tifs.2016.05.011
    1. Garrido D, Dallas DC, Mills DA. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications. Microbiology (2013) 159:649–64.10.1099/mic.0.064113-0
    1. Garrido D, Ruiz-Moyano S, Lemay DG, Sela DA, German JB, Mills DA. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci Rep (2015) 5:13517.10.1038/srep13517
    1. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr (2000) 30:61–7.10.1097/00005176-200001000-00019
    1. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature (2011) 469:543–7.10.1038/nature09646
    1. Matsuki T, Yahagi K, Mori H, Matsumoto H, Hara T, Tajima S, et al. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development. Nat Commun (2016) 7:11939.10.1038/ncomms11939
    1. Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med (2015) 7:307ra152.10.1126/scitranslmed.aab2271
    1. Mace K, Steenhout P, Klassen P, Donnet A. Protein quality and quantity in cow’s milk-based formula for healthy term infants: past, present and future. Nestle Nutr Workshop Ser Pediatr Program (2006) 58:109–203.10.1159/000095063
    1. Payne AN, Chassard C, Zimmermann M, Muller P, Stinca S, Lacroix C. The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization. Nutr Diabetes (2011) 1:e12.10.1038/nutd.2011.8
    1. Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TM, Comelli EM. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes (2014) 4:e121.10.1038/nutd.2014.23
    1. Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TM. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes (Lond) (2014) 38:1525–31.10.1038/ijo.2014.46
    1. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) (2010) 18:190–5.10.1038/oby.2009.167
    1. Teixeira TF, Grzeskowiak L, Franceschini SC, Bressan J, Ferreira CL, Peluzio MC. Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors. Br J Nutr (2013) 109:914–9.10.1017/S0007114512002723
    1. Knol J, Scholtens P, Kafka C, Steenbakkers J, Gro S, Helm K, et al. Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants. J Pediatr Gastroenterol Nutr (2005) 40:36–42.10.1097/00005176-200501000-00007
    1. Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol (2009) 11:2112–22.10.1111/j.1462-2920.2009.01931.x
    1. Sun Y, O’Riordan MX. Regulation of bacterial pathogenesis by intestinal short-chain fatty acids. Adv Appl Microbiol (2013) 85:93–118.10.1016/B978-0-12-407672-3.00003-4
    1. Garrote GL, Abraham AG, Rumbo M. Is lactate an undervalued functional component of fermented food products? Front Microbiol (2015) 6:629.10.3389/fmicb.2015.00629
    1. Rubic T, Lametschwandtner G, Jost S, Hinteregger S, Kund J, Carballido-Perrig N, et al. Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat Immunol (2008) 9:1261–9.10.1038/ni.1657
    1. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol (2014) 12:661–72.10.1038/nrmicro3344
    1. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res (2013) 54:2325–40.10.1194/jlr.R036012
    1. Vogt JA, Wolever TM. Fecal acetate is inversely related to acetate absorption from the human rectum and distal colon. J Nutr (2003) 133:3145–8.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera