Effects of prebiotics, probiotics, and synbiotics on the infant gut microbiota and other health outcomes: A systematic review

Abstract

The primary aim of this review was to systematically evaluate the literature regarding the effect of pre-, pro-, or synbiotic supplementation in infant formula on the gastrointestinal microbiota. The Cochrane methodology for systematic reviews of randomized controlled trials (RCTs) was employed. Five databases were searched and 32 RCTs (2010-2021) were identified for inclusion: 20 prebiotic, 6 probiotic, and 6 synbiotic. The methods utilized to evaluate gastrointestinal microbiota varied across studies and included colony plating, fluorescence in situ hybridization, quantitative real-time polymerase chain reaction, or tagged sequencing of the 16S rRNA gene. Fecal Bifidobacterium levels increased with supplementation of prebiotics and synbiotics but not with probiotics alone. Probiotic and synbiotic supplementation generally increased fecal levels of the bacterial strain supplemented in the formula. Across all pre-, pro-, and synbiotic-supplemented formulas, results were inconsistent regarding fecal Clostridium levels. Fecal pH was lower with some prebiotic and synbiotic supplementation; however, no difference was seen with probiotics. Softer stools were often reported in infants supplemented with pre- and synbiotics, yet results were inconsistent for probiotic-supplemented formula. Limited evidence demonstrates that pre- and synbiotic supplementation increases fecal Bifidobacterium levels. Future studies utilizing comprehensive methodologies and additional studies in probiotics and synbiotics are warranted.

Keywords: Gastrointestinal microbiota; infant; prebiotic; probiotic; synbiotic; systematic review.

Figure 1.

PRISMA 2020 diagram. An outline of studies identified, screened, and included in this systematic review.

Figure 2.

Overall bias ratings for each study: domain 1, bias arising from the randomization process; domain 2, bias due to deviations from intended interventions; domain 3, bias due to missing outcome data; domain 4, bias in measurement of the outcome; domain 5, bias in selection of the reported result. Green indicates low concern for risk of bias, yellow indicates some concern for risk of bias, and red indicates high concern for risk of bias within each domain. For the overall risk of bias, green indicates low risk, yellow indicates moderate risk, and red indicates high risk.

Figure 3.

Prebiotic (A) and probiotic (B) concentrations in each formula intervention group. Pre- and probiotic concentrations reported in studies were converted to a common unit (prebiotics: g/100 mL; probiotics: CFU/100 mL). Prebiotic abbreviations: 2’FL, 2’-fucosyllactose; BMOS, bovine milk oligosaccharide; FOS, fructooligosaccharide; GOS, galactooligosaccharide; lcFOS, long-chain FOS; LNnT, lacto-N-neotetraose; OF, oligofructose; PDX, polydextrose; scFOS, short-chain FOS; scGOS, short-chain GOS; SN-2 oil, high oleic-palmitic-oleic oil.