Supplementation with Bifidobacterium strains may modulate the faecal microbiota and metabolites of healthy infants during the first year of life

It is suspected that early-life gut microbiota colonization can result in long-lasting consequences that may increase the risk of chronic diseases in adulthood. The first 3 years of life appear to represent the most critical period for dietary interventions with the goal of manipulating microbiota to improve child growth and development and positively affect health. The role of perinatal nutrition on the infant microbiome has been gaining increasing interest, and although many studies have been carried out to determine the effects of probiotics on health in early life, few have documented in detail the effects of probiotics on the composition and function of the infant gut microbiome.

A new double-blind, randomized, placebo-controlled study, led by Prof. Dirk Haller from the ZIEL – Institute for Food & Health at Technical University of Munich (Freising, Germany), has found that supplementing the infant diet with Bifidobacterium strains may modulate both the faecal microbiota and metabolites during early life with no detectable effects on gut microbiota at 2 years of age.

From birth to 12 months of age, participants born by vaginal or caesarean delivery were randomly administered a formula diet with (n = 48) or without (n = 49) bifidobacteria, which was provided to the infants either exclusively or in parallel to breast milk. Interventional formula was based on control whey-based formula plus a total concentration of 108 colony forming units/g of 4 Bifidobacterium strains: Bifidobacterium bifidum, B. breve, B. longum and B. longum subspecies infantis. Furthermore, a third group of 9 infants was exclusively breastfed for the entire study period of 1 year. Of the 106 infants who completed the study, 70 were seen for follow-up at the age of 2 years.

Both compositional (via 16S ribosomal ribonucleic acid gene amplicon analysis) and functional (metabolomics via ultra high-performance liquid chromatography-mass spectrometry) changes were determined through the first year of life and over a period of 2 years.

Although bifidobacteria supplementation did not compensate for differences in gut microbial profiles between formula-fed and exclusively breastfed infants, infants receiving the bifidobacteria-supplemented formula showed decreased levels of Bacteroides fragilis – similar to the breastfed gut ecosystem – and Blautia species at the first month of life, whereas placebo-fed infants were more often colonized by these species. Besides this, the intervention group showed a significantly different metabolite profile compared to the placebo formula group and the exclusively breastfed group during the first year of life; this profile was driven by lipids and unknown metabolites.

Besides this, significant differences in the gut microbiota composition and metabolites were detected overall between infants fed breast milk and those fed formula, and between infants birthed vaginally and those birthed by caesarean delivery; infant feeding and type of delivery are two known factors that can influence the process of early-life colonization of the intestinal tract. However, no differences were observed between infant feeding groups regarding growth, antibiotic intake, or other health variables.

Regarding the impact of breastfeeding on the infant faecal microbiota, breastfeeding was associated with high relative abundance of B. longum, B. bifidum and Ruminococcus gnavus when compared with the formula groups. Besides this, the maternal “secretor status” -whether or not she secretes certain protective sugars in milk- determined the concentrations of both sialylated and fucosylated human milk oligosacharrides (HMOs)complex oligosaccharides that are indigestible by the infant yet specifically promote the growth of bifidobacteria- and B. longum was absent in faeces of infants breastfed by nonsecreting mothers.

The researchers also assessed whether formula-derived bifidobacteria strains were able to colonize the infant gut during and 1 year after the feeding period and with this aim the presence of supplemented bifidobacteria was assessed in faecal samples collected from infants fed probiotic formula at months 4, 12, and 24. B. bifidum, B. breve and B. longum were found in almost all samples during the intervention period with a frequency of detection in month 4 higher than in month 12. At 2 years of life, Bifidobacterium strains were not detectable. B. longum subspecies infantis was not detectable at any of the time points measured. Competitive exclusion of the strains in the intestine, loss of viability during post-delivery processing of the formula powder by the participants and antibiotic treatment are reported by the authors as factors that could influence the engraftment of administered bifidobacteria.

Faecal metabolites discriminated between interventional formula and placebo formula at the age of 1 month. Besides this, metabolites also differed between formula and breastfed groups at months 7 and 12. Most of the metabolites discriminating between exclusively breastfed, interventional formula and placebo formula were assigned to sterol lipids, glycerophospholipids, and fatty acids. These results suggest that the resident gut microbiota may impact the metabolic profile of the gut lumen, which is in agreement with previous research.

The exclusively breastfed group was associated with lower faecal proportions of propionate, butyrate, valerate, and isovalerate, whereas no significant differences in the short-chain fatty acids profile were detected between the interventional formula and placebo formula groups. Concentrations of propionic, butyric, isovaleric, and valeric acid increased over time independent of feeding group.

In conclusion, this study shows that early-life supplementation with a formula containing Bifidobacterium species may modulate specific gut commensal bacteria and metabolites during the first year of life with no detectable effects at 2 years. Further research is needed in order to elucidate health benefits of Bifidobacterium administration on bacterial and metabolite profiles.

 

Reference:

Bazanella M, Maier TV, Clavel T, et al. Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome. Am J Clin Nutr. 2017. doi: 10.3945/ajcn.117.157529.

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.