Effect of formula composition on the development of infant gut microbiota
Abstract
OBJECTIVES: Breast-feeding induces a gut microbiota rich in bifidobacteria, whereas formula-fed babies have a more diverse colonization. This ecosystem contributes to the development of the immune response and the lower incidence of diarrhea and allergy in breast-fed infants. This randomized double-blind controlled trial aimed to evaluate the bifidogenic effect of a mainly whey protein study formula low in phosphate and protein, allowing a composition closer to that of human milk. PATIENTS AND METHODS: One hundred ninety healthy infants exclusively received study formula with or without Bifidobacterium longum (BL999), or a control formula for up to 4 months. Breast-fed infants served as a reference population. Stool samples collected at 2 months of age were analyzed for bacterial counts (log colony-forming unit [CFU]/g). RESULTS: Bifidobacteria counts were significantly higher in infants receiving the study formula alone (10.0[0.8], P < 0.0001, median [interquartile range]) or with BL999 (9.8[1.4], P < 0.01) than control (9.2[3.5]), and were similar to breast-fed infants (10.1[0.4], P > 0.05). The difference between the 2 study groups was 0.16 log CFU/g (90% confidence interval [CI] [0-0.4]), within the predefined equivalence margin. Microbiota profile, as a percentage of total bacteria counts, showed about 50% Bifidobacteria, 8% Enterobacteria, and <10% Clostridia in study formulae and breast-fed infants versus 22%, 13%, and 19% in controls, respectively. There were no significant differences in growth measurements, digestive tolerance, and adverse events between groups. CONCLUSIONS: This study showed that infant formula closer resembling human milk was more bifidogenic than the control formula and led to a microbiota profile similar to that for breast-fed infants.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A formula more similar to breast milk in protein composition and phosphate amount increased Bifidobacterium proportions similarly to a formula supplemented with these bacteria.
“a formula that was more similar to breast milk, in terms of protein composition and amount of phosphate, was found to increase proportions of Bifidobacterium similar to a formula that was supplemented with these bacteria24.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [24]
Cites
Amann, R., Binder, B. J., Olson, R. J., Chisholm, S. W., Devereux, R., & Stahl, D. A. (1990) · Applied and Environmental Microbiology · doi:10.1128/aem.56.6.1919-1925.1990 · Cited by 3,998 · see citing works
Developmental microbial ecology of the neonatal gastrointestinal tract
Mackie, R. I., Sghir, A., & Gaskins, H. R. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.5.1035s · Cited by 1,360 · see citing works
Harmsen, H. J. M., Wildeboer-Veloo, A. C. M., Raangs, G. C., Wagendorp, A. A., Klijn, N., BINDELS, J. G., & Welling, G. W. (2000) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200001000-00019 · Cited by 1,326 · see citing works
Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing
Kalliomäki, M., Kirjavainen, P., Eerola, E., Kero, P., Salminen, S., & Isolauri, E. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.111237 · Cited by 1,255 · see citing works
Sudo, N., Sawamura, S., Tanaka, K., Aiba, Y., Kubo, C., & Koga, Y. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.4.1739 · Cited by 1,070 · see citing works
Langendijk-Genevaux, P. S., Schut, F., Jansen, G. J., Raangs, G. C., Kamphuis, G. R., Wilkinson, M. H. F., & Welling, G. W. (1995) · Applied and Environmental Microbiology · doi:10.1128/aem.61.8.3069-3075.1995 · Cited by 974 · see citing works
Nutritional and physiologic significance of human milk proteins
Lönnerdal, B. L. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.6.1537s · Cited by 879 · see citing works
Koletzko, B. V., Baker, S. S., Cleghorn, G. J., Neto, U. F., Gopalan, S., Hernell, O., Hock, Q. S., Jirapinyo, P., Lönnerdal, B., Pencharz, P. B., et al. (2005) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/01.mpg.0000187817.38836.42 · Cited by 662 · see citing works
Wilms, R., Sass, H., Köpke, B., Cypionka, H., & Engelen, B. (2006) · FEMS Microbiology Ecology · doi:10.1111/j.1574-6941.2006.00225.x · Cited by 437 · see citing works
The role of gut-associated lymphoid tissues and mucosal defence
Forchielli, M. L., & Walker, W. A. (2005) · British Journal Of Nutrition · doi:10.1079/bjn20041356 · Cited by 305 · see citing works
Differences in Bifidobacterium flora composition in allergic and healthy infants
Ouwehand, A. C., Isolauri, E., He, F., Hashimoto, H., Benno, Y., & Salminen, S. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.115754 · Cited by 277 · see citing works
Oligosaccharides in Human Milk and Bacterial Colonization
Newburg, D. S. (2000) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200000002-00003 · Cited by 212 · see citing works
Re‐evaluation of the whey protein/casein ratio of human milk
Kunz, C., & Lönnerdal, B. L. (1992) · Acta Paediatrica · doi:10.1111/j.1651-2227.1992.tb12184.x · Cited by 168 · see citing works
Langhendries, J. P., Detry, J., Hees, J. N. V., Lamboray, J. M., Darimont, J., Mozin, M. J., Secretin, M. C., & Senterre, J. (1995) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-199508000-00009 · Cited by 164 · see citing works
Investigation of the intestinal microbiota in preterm infants using different methods
Rougé, C., Goldenberg, O., Ferraris, L., Berger, B. W., Rochat, F., Legrand, A., Göbel, U. B., Vodovar, M., Voyer, M., Rozé, J., et al. (2010) · Anaerobe · doi:10.1016/j.anaerobe.2010.06.002 · Cited by 141 · see citing works
Self-citationKunz, C., & Lönnerdal, B. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/51.1.37 · Cited by 137 · see citing works
Effect of intestinal microbiota on the induction of regulatory CD25+ CD4+ T cells
Ishikawa, H., Tanaka, K., Maeda, Y., Aiba, Y., Hata, A., Tsuji, N. M., Koga, Y., & Matsumoto, T. (2008) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03668.x · Cited by 131 · see citing works
Intestinal microbiota and immunoglobulin E responses in 5‐year‐old Estonian children
Sepp, E., Julge, K., Mikelsaar, M., & Björkstén, B. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02315.x · Cited by 130 · see citing works
Murray, C. S., Tannock, G. W., Simon, M. A., Harmsen, H. J. M., Welling, G. W., Čustović, A., & Woodcock, A. A. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02259.x · Cited by 104 · see citing works
The Gut Microflora of the Developing Infant: Microbiology and Metabolism
Heavey, P., & Rowland, I. R. (1999) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v11i2.7887 · Cited by 64 · see citing works
The Acquisition of the Normal Microflora of the Gastrointestinal Tract
Tannock, G. W. (1994) · Springer series in applied biology · doi:10.1007/978-1-4471-3443-5_1 · Cited by 31 · see citing works
A whey-predominant formula induces fecal microbiota similar to that found in breast-fed infants
Rochat, F., Cherbut, C., Barclay, D., Puccio, G., Fazzolari-Nesci, A., Grathwohl, D., & Haschke, F. (2007) · Nutrition Research · doi:10.1016/j.nutres.2007.09.008 · Cited by 23 · see citing works
Self-citationSorrento studies of diet and fecal flora in the newborn
Wharton, B. A., Balmer, S. E., & Scott, P. H. (1994) · Pediatrics International · doi:10.1111/j.1442-200x.1994.tb03249.x · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease
Albenberg, L. G., & Wu, G. D. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.058 · Cited by 606 · see citing works
Fiocchi, A., Pawankar, R., Cuello-Garcia, C., Ahn, K., Al-Hammadi, S., Agarwal, A., Beyer, K., Burks, W., Canonica, G. W., Ebisawa, M., et al. (2015) · World Allergy Organization Journal · doi:10.1186/s40413-015-0055-2 · Cited by 473 · see citing works
Cuello-Garcia, C. A., Brożek, J. L., Fiocchi, A., Pawankar, R., Yepes-Nuñez, J. J., Terracciano, L., Gandhi, S., Agarwal, A., Zhang, Y., & Schünemann, H. J. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.04.031 · Cited by 383 · see citing works
The exposome in atopic dermatitis
Stefanovic, N., Flohr, C., & Irvine, A. D. (2020) · Allergy · doi:10.1111/all.13946 · Cited by 181 · see citing works
Soy and Gut Microbiota: Interaction and Implication for Human Health
Huang, H., Krishnan, H. B., Pham, Q., Yu, L. L., & Wang, T. T. Y. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b03725 · Cited by 138 · see citing works
Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems
Ardeshir, A., Narayan, N. R., Méndez-Lagares, G., Lu, D., Rauch, M., Huang, Y., Van Rompay, K. K. A., Lynch, S. V., & Hartigan-O’Connor, D. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008791 · Cited by 134 · see citing works
A comparison of two probiotic strains of bifidobacteria in premature infants
Underwood, M. A., Kalanetra, K. M., Bokulich, N. A., Lewis, Z. T., Mirmiran, M., Tancredi, D. J., & Mills, D. A. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.07.017 · Cited by 121 · see citing works
Mills, S., Lane, J. A., Smith, G. J., Grimaldi, K. A., Ross, R. P., & Stanton, C. (2019) · Nutrients · doi:10.3390/nu11071468 · Cited by 88 · see citing works
- Authors
- Hascoët, J., Hubert, C., Rochat, F., Legagneur, H., Gaga, S., Emady‐Azar, S., & Steenhout, P. G.
- Affiliations
- Neonatology Department France
- Nestlé (Switzerland) (CH)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Nestec (Switzerland) (CH)
- Corresponding author
- Hascoët, Jean‐Michel
- Hubert, Claire
- Gaga, Simona
- ORCID
- Hascoët, Jean‐Michel
- Venue
- Journal of Pediatric Gastroenterology and Nutrition
- Publisher
- Wiley
- Published
- 2011-06
- Volume
- 52
- Issue
- 6
- Pages
- 756-762
- ISSN
- 0277-2116 (ISSN-L)
- 1536-4801
- OpenAlex
- W2151305326
- Cited by
- 121
- References
- 23
- Citations by year
- 2025: 9 · 2024: 6 · 2023: 11 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 11 · 2014: 9 · 2013: 9 · 2012: 7
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pediatric Gastroenterology and Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- infant formula, gut microbiota, bifidogenic effect, Bifidobacterium longum, Bifidobacterium, whey protein, breast milk composition, breastfeeding, exclusive breastfeeding, infant diarrhea, infant allergy
- MeSH terms
- Bifidobacterium, Breast Feeding, Clostridium, Double-Blind Method, Enterobacteriaceae, Feces, Female, Food Microbiology, Humans, Infant, Newborn, Male, Milk, Human, Probiotics, Infant Formula, Gastrointestinal Tract, Metagenome, Bacterial Load
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
