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Additional file 3. Review history.

Additional file 2. Supplementary Figures S1 to S11.

The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases., This work was supported by the European Research Council (ERC-STG project MetaPG-716575 and ERC-CoG microTOUCH-101045015) to N.S. and by EMBO ALTF 593–2020 to M.V.-C. The work was also partially supported by MIUR ‘Futuro in Ricerca’ (grant no. RBFR13EWWI_001) to N.S., by the European H2020 programme (ONCOBIOME-825410 project, MASTER-818368 project, and IHMCSA-964590) to N.S., by the National Cancer Institute of the National Institutes of Health (1U01CA230551) to N.S., by the Premio Internazionale Lombardia e Ricerca 2019 to N.S., by the Simons Foundation (award ID 648614) to E.D. and N.S., and by the European Research Council (ERC-STG project Mami-639226) to M.C.C

The human microbiome seeding starts at birth, when pioneer microbes are acquired mainly from the mother. Mode of delivery, antibiotic prophylaxis, and feeding method have been studied as modulators of mother-to-infant microbiome transmission, but other key influencing factors like modern westernized lifestyles with high hygienization, high-calorie diets, and urban settings, compared with non-westernized lifestyles have not been investigated yet. In this study, we explored the mother-infant sharing of characterized and uncharacterized microbiome members via strain-resolved metagenomics in a cohort of Ethiopian mothers and infants, and we compared them with four other cohorts with different lifestyles. The westernized and non-westernized newborns' microbiomes composition overlapped during the first months of life more than later in life, likely reflecting similar initial breast-milk-based diets. Ethiopian and other non-westernized infants shared a smaller fraction of the microbiome with their mothers than did most westernized populations, despite showing a higher microbiome diversity, and uncharacterized species represented a substantial fraction of those shared in the Ethiopian cohort. Moreover, we identified uncharacterized species belonging to the Selenomonadaceae and Prevotellaceae families specifically present and shared only in the Ethiopian cohort, and we showed that a locally produced fermented food, injera, can contribute to the higher diversity observed in the Ethiopian infants' gut with bacteria that are not part of the human microbiome but are acquired through fermented food consumption. Taken together, these findings highlight the fact that lifestyle can impact the gut microbiome composition not only through differences in diet, drug consumption, and environmental factors but also through its effect on mother-infant strain-sharing patterns., This work was supported by the European Research Council (ERC-STG project MetaPG-716575) to N.S., by MIUR “Futuro in Ricerca” (grant no. RBFR13EWWI_001) to N.S., by the European H2020 program (ONCOBIOME-825410 project and MASTER-818368 project) to N.S., by the National Cancer Institute of the National Institutes of Health (1U01CA230551) to N.S., by the Premio Internazionale Lombardia e Ricerca 2019 to N.S., by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds, and by the EMBO ALTF 593-2020 to M.V.-C. The authors would like to acknowledge support from the European Research Council (ERC-STG project MAMI, ref. 639226) and PROMETEO GVA (ref. 012/2020) to M.C.C. and M.S.-R., respectively, and from Plan GenT project (CDEIGENT 2020) to R.C.-R. Finally, M.C.C., R.C.-R., and M.S.-R. acknowledge the award of the Spanish government MCIN/AEI to the IATA-CSIC as Center of Excellence Accreditation Severo Ochoa (CEX2021-001189-S/MCIN/AEI/10.13039/501100011033).This article is part of a project that has received funding from the European Union’s Horizon 2020 Research and Innovation Programme (GA no. 949742 ERC-HealthXCross) to R.R.

Mouse models are key tools for investigating host-microbiome interactions. However, shotgun metagenomics can only profile a limited fraction of the mouse gut microbiome. Here, we employ a metagenomic profiling method, MetaPhlAn 4, which exploits a large catalog of metagenome-assembled genomes (including 22,718 metagenome-assembled genomes from mice) to improve the profiling of the mouse gut microbiome. We combine 622 samples from eight public datasets and an additional cohort of 97 mouse microbiomes, and we assess the potential of MetaPhlAn 4 to better identify diet-related changes in the host microbiome using a meta-analysis approach. We find multiple, strong, and reproducible diet-related microbial biomarkers, largely increasing those identifiable by other available methods relying only on reference information. The strongest drivers of the diet-induced changes are uncharacterized and previously undetected taxa, confirming the importance of adopting metagenomic methods integrating metagenomic assemblies for comprehensive profiling.