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
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
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Bifidobacterium infantis | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium infantis | Increased Immunoglobulin A Levels | Beneficial | Moderate |
| Bifidobacterium infantis | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis | Safety of Bifidobacterium infantis Supplementation | Neutral | Large |
| Bifidobacterium infantis BI02 | Increased Acetic Acid in Stool | Beneficial | Moderate |
| Bifidobacterium infantis BI02 | Increased Bifidobacterium Levels | Beneficial | Large |
| Bifidobacterium infantis BI02 | Increased Stool Immunoglobulin A (IgA) | Beneficial | Moderate |
| Bifidobacterium infantis BI02 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis BI02 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium infantis BI02 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium infantis HA-116 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis HA-116 | Increased Bifidobacterium Levels | Beneficial | Large |
| Bifidobacterium infantis HA-116 | Increased Immunoglobulin A Levels | Beneficial | Moderate |
| Bifidobacterium infantis HA-116 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis HA-116 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium infantis HA-116 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium infantis M-63 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis M-63 | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium infantis M-63 | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium infantis M-63 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis M-63 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium infantis M-63 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium infantis MAK22B04I | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis MAK22B04I | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium infantis MAK22B04I | Increased Immunoglobulin A Levels | Beneficial | Moderate |
| Bifidobacterium infantis MAK22B04I | No Adverse Food Reactions | Neutral | Large |
| Bifidobacterium infantis MAK22B04I | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis MAK22B04I | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium infantis MAK22B04I | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium infantis SD-6720 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis SD-6720 | Increased Bifidobacterium Levels | Beneficial | Large |
| Bifidobacterium infantis SD-6720 | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium infantis SD-6720 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium infantis SD-6720 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium infantis SD-6720 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium infantis VPro 53 | Absence of Adverse Events | Neutral | Large |
| Bifidobacterium infantis VPro 53 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium infantis VPro 53 | Increased Bifidobacterium Abundance | Beneficial | Moderate |
| Bifidobacterium infantis VPro 53 | Increased Immunoglobulin A Levels | Beneficial | Moderate |
| Bifidobacterium infantis VPro 53 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum B1-05 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum B1-05 | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium longum B1-05 | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium longum B1-05 | No Adverse Food Reactions | Neutral | Large |
| Bifidobacterium longum B1-05 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum B1-05 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum B1-05 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium longum subsp. infantis | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium longum subsp. infantis | No Adverse Food Reactions | Neutral | Large |
| Bifidobacterium longum subsp. infantis | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum subsp. infantis | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium longum subsp. infantis M-63 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis M-63 | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium longum subsp. infantis M-63 | Increased Stool IgA Levels | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis M-63 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum subsp. infantis M-63 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum subsp. infantis M-63 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium longum subsp. longum | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium longum subsp. longum | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum subsp. longum | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium longum subsp. longum 35624 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum 35624 | Increased Fecal Secretory IgA Levels | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum 35624 | Increased Gut Bifidobacteria | Beneficial | Large |
| Bifidobacterium longum subsp. longum 35624 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum 35624 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum subsp. longum 35624 | Reduced Watery Stools | Beneficial | Small |
| Bifidobacterium longum subsp. longum UABI-14 | Increased Acetic Acid Levels in Feces | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum UABI-14 | Increased Bifidobacterium Levels | Beneficial | Large |
| Bifidobacterium longum subsp. longum UABI-14 | Increased Serum Immunoglobulin A (IgA) Levels | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum UABI-14 | Reduced Faecal pH | Beneficial | Moderate |
| Bifidobacterium longum subsp. longum UABI-14 | Reduced Frequency of Defecation | Beneficial | Small |
| Bifidobacterium longum subsp. longum UABI-14 | Reduced Watery Stools | Beneficial | Small |