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Chen et al. Microbiome Res Rep 2025;4:8 https://dx.doi.org/10.20517/mrr.2024.44 Page 7 of 18

switch to PF at various time points per infant (8 stars) .

Figure 2. Overview of studies included in this review. On the X-axis, the sampling period is shown, expressed in weeks of PMA. (A)
Subgroup A consists of studies where infants received 100% human milk (MOM/DHM); (B) Subgroup B consists of studies where
infants received a combination of human milk (MOM/DHM) and PF. Note: To express the maturity stage of infants at the time of
sample collection, we calculated PMA during sampling collection time points. For the start of the PMA range, we added the earliest time
point of sample collection to the lowest mean or median gestational age from both groups (MOM and DHM). For the end of the PMA
range, we added the latest time point of sample collection to the highest mean or median gestational age from both groups. For studies
that stated sampling at the day of achieving full enteral feeding, but not explicitly mentioning at which day of life this was, we arbitrarily
chose ten days of age as the mean age of achieving full enteral feeding in order to calculate the PMA during sample collection [38] . N
*
means number of stool samples collected at one or multiple time points. N for all time points combined. Created with Biorender.com.
PMA: Postmenstrual age; MOM: mother’s own milk; DHM: donor human milk; PF: preterm formula; GA: gestational age; DoL: day of life;
WoL: week of life; FEFA: full enteral feeding achieved.

Risk of bias and quality of the evidence
The assessment of the included cohort studies using the NOS is shown in Table 2. Four studies [31,33,34,37] had a
maximum score of 9 stars, two studies [19,36] 8 stars, and two studies [32,35] 7 stars. The representativeness of the
DHM cohort in the study by Cong et al. was limited , because there were only two or three infants at each
[36]
observed time point (the average number of stool collections in this study for each infant was 12.7). Piñeiro-
Ramos et al. and Parra-Llorca et al. only collected stool samples once when the infants reached full enteral
feeding, so those studies scored 0 on “long-enough follow-up” or “adequacy of follow-up cohort” [32,35] . The
study by Gregory et al. was characterized by a high risk of bias due to varied DHM exposure levels given the
[19]

Gut microbiome outcomes
The outcomes of this part are described under the following items:
(1) Alpha diversity (a measure of microbiome diversity within a single sample),
(2) Beta diversity (a measure of similarity of microbiota composition between groups),
(3) taxonomy,
(4) fecal metabolites, and
(5) clinical outcomes.
The MOM group serves as a reference group in text, tables, and figures, unless stated otherwise.

Alpha diversity
Subgroup A