Early development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. To study the development of the infant gut virome over time and the factors that shape it, we longitudinally assess the composition of gut viruses and their bacterial hosts in 30 women during and after pregnancy and in their 32 infants during their first year of life. Using shotgun metagenomic sequencing applied to dsDNA extracted from Virus-Like Particles (VLPs) and bacteria, we generate 205 VLP metaviromes and 322 total metagenomes. With this data, we show that while the maternal gut virome composition remains stable during late pregnancy and after birth, the infant gut virome is dynamic in the first year of life. Notably, infant gut viromes contain a higher abundance of active temperate phages compared to maternal gut viromes, which decreases over the first year of life. Moreover, we show that the feeding mode and place of delivery influence the gut virome composition of infants. Lastly, we provide evidence of co-transmission of viral and bacterial strains from mothers to infants, demonstrating that infants acquire some of their virome from their mother’s gut.

The gut microbiome is involved in the bi-directional relationship of the gut – brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut – brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

Background: The opportunistic pathogen Staphylococcus aureus is an asymptomatically carried member of the microbiome of about one third of the human population at any given point in time. Body sites known to harbor S. aureus are the skin, nasopharynx, and gut. In particular, the mechanisms allowing S. aureus to pass the gut epithelial barrier and to invade the bloodstream were so far poorly understood. Therefore, the objective of our present study was to investigate the extent to which genetic differences between enteric S. aureus isolates and isolates that caused serious bloodstream infections contribute to the likelihood of invasive disease. Results: Here, we present genome-wide association studies (GWAS) that compare the genome sequences of 69 S. aureus isolates from enteric carriage by healthy volunteers and 95 isolates from bloodstream infections. We complement our GWAS results with a detailed characterization of the cellular and extracellular proteomes of the representative gut and bloodstream isolates, and by assaying the virulence of these isolates with infection models based on human gut epithelial cells, human blood cells, and a small animal infection model. Intriguingly, our results show that enteric and bloodstream isolates with the same sequence type (ST1 or ST5) are very similar to each other at the genomic and proteomic levels. Nonetheless, bloodstream isolates are not necessarily associated with an invasive profile. Furthermore, we show that the main decisive factor preventing infection of gut epithelial cells in vitro is the presence of a tight barrier. Conclusions: Our data show that virulence is a highly variable trait, even within a single clone. Importantly, however, there is no evidence that blood stream isolates possess a higher virulence potential than those from the enteric carriage. In fact, some gut isolates from healthy carriers were more virulent than bloodstream isolates. Based on our present observations, we propose that the integrity of the gut epithelial layer, rather than the pathogenic potential of the investigated enteric S. aureus isolates, determines whether staphylococci from the gut microbiome will become invasive pathogens.

Humans and their gut microbiota have co-evolved over thousands of years, resulting in the establishment of a complex host–microbiota ecosystem. Early life environmental factors, such as delivery mode, nutrition and medication use, have been shown to substantially affect both host–microbiota interactions and health outcomes. However, the effects of urbanization (characterized by the spectrum of rural and urban populations) on these early life events have been overlooked. A deeper understanding of the relationship between urbanization and microbiota development will allow for the identification of novel biological and social approaches that can be implemented to prevent and treat disease and promote maternal and infant/child health. The aim of this review is to summarize how factors associated with urbanization differentially impact delivery mode, nutrition and medication use, and how these changes subsequently affect the gut microbiota and health outcomes of infants. This review also describes the important evidence gaps associated with these relationships and recommends actions that can be taken to improve the health of mothers and infants worldwide.

The establishment of the infant gut microbiome is critical for later health ^1,2 , yet how it is shaped by maternal and early-life factors remains unclear. Here we metagenomically sequenced 4,526 longitudinal faecal samples from 714 mother–infant pairs in the Dutch birth cohort Lifelines NEXT, spanning 12 weeks of pregnancy to 1 year postpartum. We integrated these data with 474 clinical and exposure variables, and with ultra-deep sequencing of breast milk and vaginal microbiomes. We observe that the maternal gut microbiome undergoes only subtle changes during pregnancy and postpartum, influenced by diet, infections and pre-pregnancy smoking. The maternal gut microbiome is a major reservoir for infant gut strains, with only occasional transmission from vaginal and breast milk microbiomes. Mother–infant gut strain sharing is time dependent, and higher maternal gut species abundance increases the likelihood of strain transmission. We find that the maternal gut microbiome is a predictor of infant eczema. Mode of delivery and feeding mode primarily shaped the infant gut microbiome and its functional profiles, with maternal exposures also having a role. Of 585 vaginally delivered infants, 155 were born at home, but home delivery was only moderately associated with infant gut microbiome composition, similar to other birth parameters such as duration of pushing and ruptured membranes. Overall, we highlight the central role of the mother and her microbiome in shaping the infant gut ecosystem and early health outcomes.

Emerging evidence suggests a bidirectional relationship between sleep and the gut microbiome. In this study, we explore the associations of sleep characteristics with lifestyle factors and gut microbiome composition in 6941 participants from the Lifelines Dutch Microbiome Project. We show that lower alpha diversity is associated with poorer sleep quality, later chronotype, and greater social jet lag, while beta diversity is linked to both sleep quality and social jet lag. Of the 137 bacterial species associated with sleep, 35.6% are validated in an independent cohort. Mediation analyses indicate that, while changes in species abundance are largely a consequence of sleep behavior, certain species may mediate diet’s influence on sleep. For example, we find that Clostridia species UC5_1_1E11 and SGB14844 mediate the effect of coffee intake on social jet lag. These findings highlight the intricate relationship between diet, the gut microbiome, and sleep, suggesting the potential for microbiome-targeted interventions to improve sleep health.