Early Probiotic Supplementation of Healthy Term Infants with Bifidobacterium longum subsp. infantis M-63 Is Safe and Leads to the Development of Bifidobacterium-Predominant Gut Microbiota: A Double-Blind, Placebo-Controlled Trial

2023-03-14
Nutrients 15(6)
- A. Hiraku
- Setsuko Nakata
- Mai Murata
- Chendong Xu
- N. Mutoh
- Satoshi Arai
- T. Odamaki
- N. Iwabuchi
- Miyuki Tanaka
- Takahisa Tsuno
- Masahiko Nakamura

PubMed: 36986131
DOI: 10.3390/nu15061402

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 110
Population: Healthy term infants
Methods: Randomized Controlled Trial

Abstract

Bifidobacteria are important intestinal bacteria that provide a variety of health benefits in infants. We investigated the efficacy and safety of Bifidobacterium longum subsp. infantis (B. infantis) M-63 in healthy infants in a double-blind, randomized, placebo-controlled trial. Healthy term infants were given B. infantis M-63 (n = 56; 1 × 109 CFU/day) or placebo (n = 54) from postnatal age ≤ 7 days to 3 months. Fecal samples were collected, and fecal microbiota, stool pH, short-chain fatty acids, and immune substances were analyzed. Supplementation with B. infantis M-63 significantly increased the relative abundance of Bifidobacterium compared with the placebo group, with a positive correlation with the frequency of breastfeeding. Supplementation with B. infantis M-63 led to decreased stool pH and increased levels of acetic acid and IgA in the stool at 1 month of age compared with the placebo group. There was a decreased frequency of defecation and watery stools in the probiotic group. No adverse events related to test foods were observed. These results indicate that early supplementation with B. infantis M-63 is well tolerated and contributes to the development of Bifidobacterium-predominant gut microbiota during a critical developmental phase in term infants.

Keywords: Bifidobacterium longum subsp. Infantis; GI motility; gut microbiota; probiotics; secretory IgA; short-chain fatty acids; term infant.

Research Insights

Bifidobacterium infantis MAK22B04I→Increased Acetic Acid Levels in Feces
Supplementation with B. infantis M-63 led to increased levels of acetic acid at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis MAK22B04I→Increased Gut Bifidobacteria
Supplementation with B. infantis M-63 significantly increased the relative abundance of Bifidobacterium compared with the placebo group.
Effect
Beneficial
Effect size
Large
Bifidobacterium infantis MAK22B04I→Increased Immunoglobulin A Levels
Supplementation with B. infantis M-63 led to decreased stool pH and increased levels of acetic acid and IgA in the stool at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis MAK22B04I→No Adverse Food Reactions
No adverse events related to test foods were observed.
Effect
Neutral
Effect size
Large
Bifidobacterium infantis MAK22B04I→Reduced Faecal pH
Supplementation with B. infantis M-63 led to decreased stool pH at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis MAK22B04I→Reduced Frequency of Defecation
There was a decreased frequency of defecation in the probiotic group.
Effect
Beneficial
Effect size
Small
Bifidobacterium infantis MAK22B04I→Reduced Watery Stools
There was a decreased frequency of watery stools in the probiotic group.
Effect
Beneficial
Effect size
Small
Bifidobacterium infantis VPro 53→Absence of Adverse Events
No adverse events related to test foods were observed.
Effect
Neutral
Effect size
Large
Bifidobacterium infantis VPro 53→Increased Acetic Acid Levels in Feces
Supplementation with B. infantis M-63 led to increased levels of acetic acid at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis VPro 53→Increased Immunoglobulin A Levels
Supplementation with B. infantis M-63 led to decreased stool pH and increased levels of acetic acid and IgA in the stool at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis VPro 53→Reduced Faecal pH
Supplementation with B. infantis M-63 led to decreased stool pH at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium longum infantis M-63→Increased Fecal Acetate Levels
and increased levels of acetic acid
Effect
Beneficial
Effect size
Small
Bifidobacterium longum infantis M-63→Increased Fecal Secretory IgA Levels
Supplementation with B. infantis M-63 led to increased levels of IgA in the stool at 1 month of age compared with the placebo group.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium longum infantis M-63→Reduced Stool Frequency
There was a decreased frequency of defecation and watery stools in the probiotic group
Effect
Beneficial
Effect size
Small
Bifidobacterium longum infantis M-63→Reduced Stool pH
B. infantis M-63 led to decreased stool pH
Effect
Beneficial
Effect size
Small