Rubinstein Rebecca J, Herrera Roberto, Vielot Nadja A, Toval Christian, Gutiérrez Lester, Reyes Yaoska, Blandón Patricia, Bowman Natalie M, Chaves-Olarte Esteban, Bucardo Filemón, Sandler Robert S, Edwards Jessie, Bode Lars, Becker-Dreps Sylvia, Vilchez Samuel
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Am J Clin Nutr. 2025 Aug;122(2):488-501. doi: 10.1016/j.ajcnut.2025.06.009. Epub 2025 Jun 12.
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.
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.
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.
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.
空肠弯曲菌和结肠弯曲菌是全球细菌性急性肠胃炎的主要病因，与儿童营养不良有关。人乳寡糖（HMOs）可作为空肠弯曲菌/结肠弯曲菌的“诱饵受体”，并通过促进肠道微生物群预防感染，从而预防弯曲菌病。
采用高效液相色谱法测定产后约1.3个月（范围0.3 - 3.2个月）母乳中19种丰富的HMOs。我们每周对儿童进行腹泻随访，并使用聚合酶链反应和桑格测序法检测腹泻粪便中的空肠弯曲菌/结肠弯曲菌。然后，我们根据HMO浓度、母婴分泌型表型以及对断奶儿童进行删失处理，评估空肠弯曲菌/结肠弯曲菌肠胃炎风险。
在409名儿童中，47名（12%）在24个月内经历了≥1次空肠弯曲菌/结肠弯曲菌肠胃炎发作。观察到丰富的中性HMO乳糖 - N - 新四糖（LNnT）[风险差（RD）-0.273（95%置信区间（CI）：-0.542，-0.004）]和唾液酸乳糖 - N - 四糖c（LSTc）[RD -0.176（95% CI：-0.363，-0.012），LNnT的唾液酸化衍生物]有很强的保护关联，但如假设的那样，丰富的α-1,2岩藻糖基化的2'-岩藻糖基乳糖（2'FL）[RD 0.067（95% CI：-0.023，0.157）]没有。乳糖 - N - 岩藻五糖 - III（LNFP - III），[RD -0.075（95% CI：-0.155，0.005）]，LNnT的另一种衍生物在敏感性分析中也有较弱的保护作用。大多数其他HMOs与空肠弯曲菌/结肠弯曲菌肠胃炎无关联或呈正相关。
在这个前瞻性出生队列中，婴儿早期摄入高浓度的2'FL对空肠弯曲菌/结肠弯曲菌肠胃炎没有保护作用。然而，高浓度的LNnT和LSTc，以及可能的LNFP - III可能与空肠弯曲菌/结肠弯曲菌肠胃炎发病率降低有关，值得作为预防母乳喂养和配方奶喂养儿童空肠弯曲菌/结肠弯曲菌肠胃炎的潜在补充剂进行研究。对于肠道感染流行地区，需要对作为补充剂的HMOs进行安全性测试。
