Human milk oligosaccharides and Campylobacter jejuni and Campylobacter coli gastroenteritis risk in a Nicaraguan Birth Cohort

Abstract

Background: Campylobacter jejuni and C. coli, leading causes of bacterial acute gastroenteritis worldwide, are associated with childhood malnutrition. Human milk oligosaccharides (HMOs) may prevent campylobacteriosis by acting as "decoy receptors" for C. jejuni/coli and by promoting gut microbiota that prevent infection.

Methods: Nineteen abundant HMOs in human milk were measured at ∼1.3 mo postpartum (range 0.3-3.2 mo) with high-performance liquid chromatography. We followed children weekly for diarrhea and used polymerase chain reaction and Sanger sequencing to detect C. jejuni/coli in diarrheic stool. We then assessed C. jejuni/coli gastroenteritis risk by HMO concentrations, maternal and child secretor phenotype, and with censoring of weaned children.

Results: Of 409 children, 47 (12%) experienced ≥1 episode of C. jejuni/coli gastroenteritis over 24 mo. Strong protective associations were observed for the abundant, neutral HMO lacto-N-neotetraose (LNnT) [RD -0.273 (95% confidence interval (CI): -0.542, -0.004)] and sialyllacto-N-tetraose c (LSTc) [RD -0.176 (95% CI: -0.363, -0.012)], a sialylated derivative of LNnT, but not the abundant α-1,2 fucosylated 2'-fucosyllactose (2'FL) [RD 0.067 (95% CI: -0.023, 0.157)], as hypothesized. Lacto-N-fucopentaose-III (LNFP-III), [RD -0.075 (95% CI: -0.155, 0.005)], another derivative of LNnT was also weakly protective in sensitivity analyses. Most other HMOs were unassociated or positively associated with C. jejuni/coli gastroenteritis.

Conclusions: Consuming high concentrations of 2'FL early in infants' lives was not protective against C. jejuni/coli gastroenteritis in this prospective birth cohort. However, high concentrations of LNnT and LSTc, and possibly LNFP-III may be associated with decreased C. jejuni/coli gastroenteritis and warrant investigation as potential supplements for C. jejuni/coli gastroenteritis prevention in chest-fed and formula-fed children. Safety testing for HMOs as supplements is needed for regions with prevalent enteric infections.

Keywords: Campylobacter coli; Campylobacter jejuni; Nicaragua; children; cohort study; diarrhea; gastroenteritis; human milk; human milk oligosaccharides.