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Impact of early life diet on microbiome development & later health

JPI HDHL “Intestinal Microbiomics” (IM2015)
Impact of early life diet on microbiome development & later health
Miguel Gueimonde
Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC)


Partner Organization Partner Country
Wageningen UniversityThe Netherlands
University College CorkIreland
Complutense University of MadridSpain
Università degli Studi di ParmaItaly

1. Overall project description

1.1 Summary

Microbial colonization of the new-born is essential for the development of the physiological homeostasis of the host. Perturbations of early-life colonization may have long-lasting effects on host health; specific alterations seem to precede the development of disease, including both communicable and non-communicable diseases. Thus, early microbiota establishment has a profound effect on long-term well-being, therefore representing a critical opportunity for microbiota modulation. Perhaps with the exception of delivery mode and breast/formula-feeding, little was known about the influence of early-life factors on the microbiota establishment. In this context the EarlyMicroHealth project aimed at at unravelling the process of intestinal microbiota establishment in infants and to deduce ways to positively modulate this process. This was done by a longitudinal cohort study, evaluating factors, such as gestational age, antibiotics exposure, etc., that negatively impact early-life microbiota development and the impact of diet and nutrition during the first years of life in driving this process. In a second step the impact of interventions, such as omega three fatty acids or probiotics, in minimizing the impact of these factors was assessed. To achieve this aim we formed a multidisciplinary consortium comprising 5 partners from 4 European countries representing: microbiologists, nutritionists, neonatologists, paediatricians, experts in OMICs and Next-Generation Sequencing and bio-informaticians. The exhaustive analyses of the infant microbiome (including phageome, resistome, etc.) and its combination and integration with clinical and nutritional data allowed determining the impact of different early factors on the microbiota development. The knowledge and tools generated within the project offer opportunities for a stronger European Research Area and increasing European competitiveness on the development and commercialization of microbiota-modulating products for infancy.

1.2 Highlights

The project has studies the impact of early factors, feeding and postweaning nutrition on the development of the microbiome. By doing this the project has;

- Developed bioinformatic tools for ITS-based profiling of Bifidobacterium genus species/subspecies and for phageome analyses.
- Developed food composition tables for commercial foods targeted to infants between 0 and 12 months of age.
- Identified by first time a phase variation shufflon in bifidobacteria
- Identified differences on microbiota development between preterm and fullterm neonates
- Unravelled the effects of intrapartum antimicrobial prophylaxis on the neonatal microbiome
- Determined the impact of antibiotic exposure during the 1st year of life on microbiome development.
- Demonstrated the vertical transmission of microorganisms and bacteriophages,
- Underlined the relationship between early microbiota and weight gain in preterm infants.
- Determined the interaction nutrition-microbiome development during the first years of life.

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Arboleya, S., Sánchez, B., Solís, G., Fernández, N., Suárez, M., Hernández-Barranco, A.M., Milani, C., Margolles, A., de Los Reyes-Gavilán, C.G., Ventura, M., Gueimonde M.Impact of Prematurity and Perinatal Antibiotics on the Developing Intestinal Microbiota: A Functional Inference Study10.3390/ijms17050649
Duranti, S., Gaiani, F., Mancabelli, L., Milani, C., Grandi, A., Bolchi, A., Santoni, A., Lugli, G., Ferrario, C., Mangifesta, M., Viappiani, A., Bertoni, S., Vivo, V., Serafini, F., Barbaro, M. R., Fugazza, A., Barbara, G., Gioiosa, L., Palanza, P., Cantoni, A. M., de'Angelis, G.L., Barocelli, E., de' Angelis, N., van Sinderen, D., Ventura, M., Turroni, F. 2016. Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers.10.1093/femsec/fiw191
Ruiz, L., Moles, L., Gueimonde, M., Rodriguez, J.M. Perinatal microbiomes’s influence on preterm birth and preterms’s health: influencing factors and modulation strategies.10.1097/MPG.0000000000001196
Gómez, M., Moles, L., Melgar, A., Ureta, N., Bustos, G., Fernández, L., Rodríguez, J.M., Jiménez, E.Early gut colonization of preterm infants. Effect of enteral feeding tubes10.1097/MPG.0000000000001104
Lugli, G.A., Milani, C., Mancabelli, L., Turroni, F., Ferrario, C., Duranti, S., van Sinderen, D., Ventura, M.Ancient bacteria of the Ötzi's microbiome: a genomic tale from the Copper Age10.1128/AEM.02894-16
Arboleya S., Martinez-Camblor P., Solis G., Suárez M., Fernández N., de los Reyes-Gavilán C.G., Gueimonde M.Intestinal microbiota and weight-gain in preterm neonates10.3389/fmicb.2017.00183
Bottacini, F., van Sinderen, D., Ventura, M.Omics of bifidobacteria: Research and insights into their health promoting activities10.1042/BCJ20160756
Brodmann T., Endo A., Gueimonde M., Vinderola G., Kneifel W., De Vos W.M., Salminen S., Gómez-Gallego C.Safety of Novel Microbes for Human Consumption: Practical Examples of Assessment in the European Union10.3389/fmicb.2017.01725
Duranti, S., Ferrario, C., van Sinderen, D., Ventura, M., Turroni, F.Duranti, S., Ferrario, C., van Sinderen, D., Ventura, M., Turroni, F.10.1186/s12263-017-0566-2
Duranti, S., Lugli, G.A., Mancabelli, L., Armanini, F., Turroni, F., James, K., Ferretti, K., Gorfer, V., Ferrario, C., Milani, C., Mangifesta, M., Anzalone, R., Zolfo, M., Viappiani, A., Pasolli, E., Bariletti, I., Canto, R., Clementi, R., Cologna, M., Crifò, T., Cusumano, G., Fedi, S., Gottardi, S., Innamorati, C., Masè, C., Postai, D., Savoi, D., Soffiati, M., Tateo, S., Pedrotti, A., Segata, N., Van Sinderen, D., Ventura, M.Maternal inheritance of bifidobacterial communities and bifidophages in infants through vertical transmission10.1186/s40168-017-0282-6
Turroni, F., Milani, C., Duranti, S., Ferrario, C., Lugli, G.A., Mancabelli, L., van Sinderen, D., Ventura, M.Bifidobacteria and the infant gut: an example of co-evolution and natural selection10.1007/s00018-017-2672-0
Valdes L., Ruas-Madiedo P., Gueimonde M.In vitro fermentation of different fructo-oligosaccharides by Bifidobacterium strains for the selection of synbiotic combinations10.1016/j.ijfoodmicro.2016.11.011
Nogacka, A., Salazar, N., Suárez, M., Milani, C., Arboleya, S., Solís, G., Fernández, N., Alaez, Hernández-Barranco, A., de los Reyes-Gavilán, C., Ventura, M., Gueimonde, M.Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic-resistance genes in vaginally delivered full-term neonates10.1186/s40168-017-0313-3
Duranti, S., Mangifesta, M., Lugli, G.A., Turroni, F., Anzalone, R., Milani, C., Mancabelli, L., Ossiprandi, M.C., Ventura, M.Bifidobacterium vansinderenii sp. nov. isolated from faeces of emperor tamarin (Saguinus imperator)10.1099/ijsem.0.002243
Ferrario, C., Statello, R., Carnevali, L., Mancabelli, L., Milani, C., Mangifesta, M., Duranti, S., Lugli, G.A., Jimenez, B., Lodge, S., Viappiani, A., Alessandri, G., Dall'Asta, M., Del Rio, D., Sgoifo, A., Van Sinderen, D., Ventura, M., Turroni, F.How to feed the mammalian gut microbiota: bacterial and metabolic modulation by dietary fibers10.3389/fmicb.2017.01749
Lugli, G.L., Milani, C., Turroni, F., Duranti, S., Mancabelli, L., Mangifesta, M., Ferrario, C., Modesto, M., Mattarelli, P., Jiří, J., van Sinderen, D., Ventura, M.Comparative genomic and phylogenomic analyses of the Bifidobacteriaceae family10.1186/s12864-017-3955-4
Mancabelli, L., Milani, C., Lugli, G.A., Turroni, F., Ferrario, C., van Sinderen, D., Ventura, M.Meta-analysis of the human gut microbiome from urbanized and pre-agricultural populations. Environ10.1111/1462-2920.13692
Mancabelli, L., Milani, C., Lugli, G.A., Turroni, F., Mangifesta, M., Viappiani, A., Ticinesi, A., Nouvenne, A., Meschi, T., van Sinderen, D., Ventura, M.Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses10.1038/s41598-017-10663-w
Milani, C., Duranti, S., Bottacini, F., Casey, E., Turroni, F., Mahony, J., Belzer, C., Delgado, S., Arboleya, S., Mancabelli, L., Lugli, G.A., Rodriguez, J.M., Bode, L., de Vos, W., Gueimonde, M., Margolles, A., van Sinderen, D., Ventura, M.The first microbial colonizers of the human gut: composition, activities and health implications of the infant gut microbiota10.1128/MMBR.00036-17
Milani, C., Mangifesta, M., Mancabelli, L., Lugli, G.A., James, K., Duranti, S., Turroni, F., Ferrario, C., Ossiprandi, M.C., van Sinderen, D., Ventura, MUnveiling bifidobacterial biogeography across the mammalian branch of the tree of life10.1038/ismej.2017.138
Milani, C., Mangifesta, M., Mancabelli, L., Lugli, G.A., Mancino, W., Viappiani, A., Faccini, A., van Sinderen, D., Ventura, M., Turroni, F.The sortase-dependent fimbriome of the genus Bifidobacterium: extracellular structures with potential to modulate microbe-host dialogue.10.1128/AEM.01295-17
Ravi A., Valdes-Varela L., Borges P.J.A., Gueimonde M., Rudi, K.Transmission and persistence of IncF conjugative plasmids in the gut microbiota of full term infants10.1093/femsec/fix158
Milani, C., Casey, E., Lugli, G.A., Moore, R., Kaczorowska, J., Feehily, C., Mangifesta, M., Mancabelli, L., Duranti, S., Turroni, F., Mahony, J., Cotter, P.J., McAuliffe F., van Sinderen, D., Ventura, M.Tracing mother-infant transmission of bacteriophages by means of a novel tool for analysis of shotgun metagenomics datasets: METAnnotatorX10.1186/s40168-018-0527-z
Díaz M, Guadamuro L, Espinosa-Martos I, Mancabelli L, Jiménez S, Molinos-Norniella C, Pérez-Solis D, Milani C, Rodríguez JM, Ventura M, Bousoño C, Gueimonde M, Margolles A, Díaz JJ, Delgado SMicrobiota and derived parameters in fecal samples of infants with non-IgE cow's milk protein allergy under a restricted diet10.3390/nu10101481
De Andrés J, Manzano S, García C, Rodríguez JM, Espinosa-Martos I, Jiménez E.Modulatory effect of three probiotic strains on infants' gut microbial composition and immunological parameters on a placebo-controlled, double-blind, randomised study10.3920/BM2017.0132
Lugli, G.A., Mancino, W., Milani, C., Duranti, S., Turroni, F., van Sinderen, D., Ventura, M.Reconstruction of the bifidobacterial pan-secretome reveals the network of extracellular interactions between bifidobacteria and the infant gut10.1128/AEM.00796-18
Rodríguez JM, Guarner F, Álvarez-Calatayud G, Suárez E.The autochthonous microbiota and probiotics: efficacious complements in the fight against infections and the rising of antibiotic resistance10.11.59/000487036
Lugli, G.A., Milani, C., Duranti, S., Alessandri, G., Turroni, F., Mancabelli, L., Tatoni, D., Ossiprandi, M.C., van Sinderen, D., Ventura, M.Isolation of novel gut bifidobacteria using a combination of metagenomic and cultivation approaches10.1186/s13059-019-1711-6
Escribano E , Zozaya C, Madero R; Sánchez L, van Goudoever J , Rodríguez JM, Sáenz de Pipaon M.Increased incidence of necrotizing enterocolitis associated with routine administration of InfloranTM in extremely preterm infants10.3920/BM2017.0098
Nogacka A., Salazar N., Arboleya S., Suárez M., Fernández N., Solís G., de los Reyes-Gavilán C.G., Gueimonde M.Early microbiota, antibiotics and health0.1007/s00018-017-2670-2
Casey E, van Sinderen D, Mahony J.In Vitro Characteristics of Phages to Guide 'Real Life' Phage Therapy Suitability10.3390/v10040163
Arboleya S, Suárez M, Fernández N, Mantecón L, Solís G, Gueimonde M, de Los Reyes-Gavilán CGC-section and the neonatal gut microbiome acquisition: consequences for future health10.1159/000490843
de Andrés J, Jiménez E, Espinosa-Martos I, Rodríguez JM, García-Conesa MTAn exploratory search for potential molecular targets responsive to the probiotic Lactobacillus salivarius PS2 in women with mastitis: gene expression profiling vs. interindividual variability10.3389/fmicb.2018.02166
Mahony J, Lugli GA, van Sinderen D, Ventura M.Impact of gut associated bifidobacteria and their phages on health: two sides ofthe same coin?10.1007/s00253-018-8795-x
Geerlings SY, Kostopoulos I, de Vos WM, Belzer C.Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?10.3390/microorganisms6030075
Mavrich TN, Casey E, Oliveira J, Bottacini F,James K, Franz CMAP, Lugli GA, Neve H, Ventura M, Hatfull GF, Mahony J, van Sinderen D.Characterization and induction of prophages in human gut-associated Bifidobacterium hosts10.1038/s41598-018-31181-3
Lugli, G.A., Mancino, W., Milani, C., Duranti, S., Mancabelli, L., Napoli, S., Mangifesta, M., Viappiani, A., Anzalone, R., Longhi, G., van Sinderen, D., Ventura, M., Turroni, F.Dissecting the evolutionary development of the Bifidobacterium animalis species through comparative genomics analyses10.1128/AEM.02806-18
Gómez-Martín, M., Arboleya, S., Gueimonde, M., Gonzalez, S.Nutritional composition of processed baby food targeted at infants from 0-12 months10.1016/j.jfca.2019.03.009
Lugli, G.A., Duranti, S., Albert, K., Mancabelli, L., Napoli, S., Viappiani, A., Anzalone, R., Longhi, G., Milani, C., Turroni, F., Alessandri, G., Sela, D., van Sinderen, D., and Ventura, M.Unveiling genomic diversity among members of the Bifidobacterium pseudolongum species, a widely distributed gut commensal of the animal kingdom10.1128/AEM.03065-18
Lugli, G.A., Mangifesta, M., Mancabelli, L., Milani, C., Turroni, F., Viappiani, A., van Sinderen, D., Ventura, M.Compositional assessment of bacterial communities in probiotic supplements by means of metagenomic techniques10.1016/j.ijfoodmicro.2019.01.011
Ventura, M., Milani, C., Lugli, G.A., van Sinderen D.Health benefits conferred by the human gut microbiota during infancy10.1111/1751-7915.13334

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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This project has received funding from the European Union’s
H2020 Research and Innovation Programme under grant agreement n.696300

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