## 2 Materials and Methods
### Studies Involved  
Three studies were identified and included in the present evaluation: [PERSON] et al., 2017 [7], [PERSON] et al. [8], and [PERSON] et al., 2020 [12], all of them being placebo, double-blind, randomized controlled trials with a parallel design. The main aim of the newborn study [12] was to address the impact of the investigational product (FM-CBA L74) on immune defense mechanisms (anticribobial peptides, s- IgA), the microbiota and its metabolome, while that in the two young infant studies [7; 8] the focus was on intake of the investigational product and reducing common infectious diseases in children attending daycare or preschool. In the newborn study three various groups were defined: breastfed, standard formula fed (based on cow's milk), and fermented formula fed. In the present study, the standard formula fed was taken as reference and evaluated against the fermented formula fed. As a reference group in the young children study a maltodextrin control was applied. Please find the various details listed in Table 1.  
The following exclusion criteria were used in the respective studies:  
* [PERSON] [7] and [PERSON] [8]:
* age below 12 months or above 48 months. * concomitant chronic infections, chronic systemic diseases, chronic inflammatory bowel diseases, autoimmune diseases, immunodeficiency, malignancy, metabolic diseases, chronic respiratory tract diseases including respiratory allergies and cystic fibrosis, \begin{table}
\begin{tabular}{l l l l} \hline \hline \multicolumn{1}{c}{**Characteristic**} & \multicolumn{1}{c}{**[PERSON] et al., 2017**} & \multicolumn{1}{c}{**[PERSON] et al., 2017**} & \multicolumn{1}{c}{**[PERSON] et al., 2020**} \\ \hline Target group & healthy children & healthy children & healthy newborns \\ Age & 12–48 months & 12–48 months & 0–7 days \\ Number of participants & postbiotic: 66; control 60 & postbiotic: 137; control 122 & postbiotic: 13; control 13 \\ Male percentage & postbiotic: 53; control 62 & postbiotic: 51; control 51 & postbiotic: 46; control 24 \\ Postbiotic & fermented cow’s milk & fermented cow’s milk & fermented cow’s milk \\ Placebo & carbohydrate controlled & carbohydrate controlled & carbohydrate controlled \\ Energy (kcal) & postbiotic: 367; control: 388 & postbiotic: 367; control: 388 & postbiotic: 367; control: 388 \\ -proteins & postbiotic: 24; control: 0 & postbiotic: 24; control: 0 & postbiotic: 24; control: 0 \\ (g/100 g product) & postbiotic: 66; control: 97 & postbiotic: 66; control: 97 & postbiotic: 66; control: 97 \\ -fat & postbiotic: 0.6; control: 0.0 & postbiotic: 0.6; control: 0.0 & postbiotic: 0.6; control: 0.0 \\ Duration (months) & 3 & 3 & 3 \\ Number of lefts & 3 & 1 & 1 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Main features of the studies considered in the analysis. malformations of gastrointestinal or urinary or respiratory tract, history of respiratory or gastrointestinal or urinary tract surgery, congenital cardiac defects, functional bowel disorders, suspected or challenge-proved food allergy, food intolerances, severe malnutrition (z-score for weight-for-height) and use of antibiotics or pre/pro/synbiotics or immune stimulating products in the 2 weeks before the enrolment. [PERSON] (2012):  
the presence of congenital diseases, chromosomal abnormalities, and/or conditions that could interfere with growth, such as brain, metabolic, cardiac and gastrointestinal diseases, perinatal infections, being born to a mother affected by endocrine and/or metabolic diseases or having a family history of allergic disease. Preparation of the investigated product. The preparation of the product was already described in various papers. In short: the basis of the product was skimmed milk fermented with _L. paracasi_ CBA L74, which was isolated from the feces of healthy infants. The fermentation was initiated with appr. 1.0 \(\times\) 10\({}^{6}\) colony-forming units (CFU) and stopped when reaching appr. 5.9 \(\times\) 10\({}^{9}\) CFU/g (after a 15 h incubation at 37 \({}^{\circ}\)C).