Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa. This Review provides an overview of SCFAs’ roles and functions, and of SCFA-producing bacteria, from their microbiological characteristics and taxonomy to the biochemical process that lead to the release of SCFAs. Moreover, we will describe the potential therapeutic approaches to boost the levels of SCFAs in the human gut and treat different related diseases.

Resistance to antibiotics is becoming a worldwide threat as infections caused by multidrug-resistant pathogenic microorganisms can overcome antibiotic treatments and spread quickly in the population. In the context of early life, newborns are at increased risk as their immune system is still under development, so infections and acquisition of resistance during childhood have short- and long-term consequences for the health. The moment of birth is the first exposure of infants to possible antibiotic-resistant microorganisms that may colonize their gut and other body sites. Different factors including mode of delivery, previous antibiotic exposure of the mother, gestational age and consumption of antibiotics in early-life have been described to modulate the neonate’s microbiota, and thus, the resistome. Other factors, such as lactation, also impact the establishment and development of gut microbiota, but little is known about the role of breastmilk in transferring Antibiotic Resistant Genes (ARG). A deeper understanding of vertical transmission of antibiotic resistance from mothers to their offspring is necessary to determine the most effective strategies for reducing antibiotic resistance in the early life. In this review, we aim to present the current perspective on antibiotic resistances in mother-infant dyads, as well as a new insight on the study of the human gut and breastmilk resistome, and current strategies to overcome this public health problem, toward highlighting the gaps of knowledge that still need to be closed.

Early life represents a critical window for metabolic, cognitive and immune system development, which is influenced by the maternal microbiome as well as the infant gut microbiome. Antibiotic exposure, mode of delivery and breastfeeding practices modulate the gut microbiome and the reservoir of antibiotic resistance genes (ARGs). Vertical and horizontal microbial gene transfer during early life and the mechanisms behind these transfers are being uncovered. In this review, we aim to provide an overview of the current knowledge on the transfer of antibiotic resistance in the mother-infant dyad through vertical and horizontal transmission and to highlight the main gaps and challenges in this area.

Virulence expression in the enteroaggregative Escherichia coli strain 042 requires the transcriptional activator AggR. We show in this report that, as reported for other virulence factors, the nucleotide second messenger (p)ppGpp is needed for a high expression level of AggR. As expected from these findings, expression of AggR-activated genes such as the AafA pilin subunit is downregulated in the absence of (p)ppGpp. Considering the fact that biofilm formation in strain 042 requires the AafA protein, biofilm development in strain 042 is impaired in derivatives that lack either the AggR protein, the virulence plasmid that encodes AggR (pAA2) or the ability to synthesize (p)ppGpp. These results show a direct correlation between (p)ppGpp, expression of AggR and biofilm development in strain 042.

Human milk metals and metalloids are variable and significantly correlate with infant gut microbiota abundance and alpha diversity indices.

Enterococcus spp. some of which are pathogenic, are common gut microbiota members, including also infants. Infants may be more susceptible to Enterococcus due to their developing gut ecosystems. It is unclear whether antibiotic resistance genes (ARGs) and certain genomic traits in enterococci are restricted to the human subpopulation or more widespread. Furthermore, the correlation between these traits and geographic variation is poorly understood. Therefore, we sequenced 100 strains isolated from full-term healthy infants' fecal samples from two geographically distant European cohorts (MAMI in Spain and LucKi from the Netherlands) to explore the diversity of Enterococcus spp. within the infant's gut microbiome and assess cohort-specific traits such as ARGs. Most isolates were E. faecalis and E. gallinarum, with a total of 11 species identified. We found a rich reservoir of ARGs, plasmids, prophages and virulence factors in the infant strains, with minimal cohort-specific differences in resistome profiles. In addition, Epx, a pore-forming toxin associated with pathogenicity, was found in E. hirae strains. While metabolic profiles were similar across cohorts, E. faecalis strains harbored more virulence genes and prophages compared to other species. An analysis of public Enterococcus genomes revealed that multi-drug resistant (MDR) strains exist without any significant geographic or temporal pattern. Phenotypic resistance analysis indicated that 28% of MAMI strains were gentamicin resistant, compared to 5% of the strains from the LucKi cohort, though LucKi isolates were also resistant to other antibiotics. We also selected ten E. faecalis isolates with varying virulence gene repertoires for phenotypic virulence testing in Caenorhabditis elegans and found them killing at various rates, however no clear pattern emerged in correlation with any specific genetic determinant. Overall, our results suggest that Enterococcus spp. including ARGs, are highly mobile across Europe and beyond. Their adaptability likely facilitates long-distance dissemination, with strains being acquired early in life from community environments.