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This technical review, one of five developed by the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) special interest group (SIG) on gut microbiota and modifications (GMM), supports the creation of a position paper on the use of biotic-supplemented formulas, including those containing human milk oligosaccharides (HMOs) produced through chemical synthesis or microbial biotechnology. Though these oligosaccharides are identical to the HMOs found in human milk, they do not originate from it. Therefore, we used human-identical milk oligosaccharides (HiMOs). This review focuses on the clinical outcomes related to the supplementation of infant formulas with these HiMOs. The ESPGHAN SIG-GMM conducted a systematic review to evaluate the clinical outcomes of HiMO-supplemented infant formulas in healthy infants (0–12 months) published before 2024. Six RCTs and two mechanistic substudies met the inclusion criteria and investigated different combinations of HiMOs added to the formula. The HiMOs studied so far show no difference compared to the control formula in outcomes such as: anthropometric data, regurgitation-related symptoms, crying, fussiness, or colic. A specific combination of five HMO-analogues (2′fucosyllactose [FL], 3-FL, lacto-N-tetraose [LNT], 3′-sialyllactose [SL], and 6′-SL) suggest a softer stool consistency and more frequent defecation in presumable healthy infants, but these studies also used the highest amount of HiMOs; however, the clinical relevance of this finding remains uncertain. Regarding infection prevention, no clear conclusion can be drawn. There was no difference in tolerability and no safety concerns were raised with the HiMO studied so far. This technical report serves as the background for formulating recommendations on the use of HiMOs-supplemented infant formula in healthy infants studied so far.