Resistome expansion in disease-associated human gut microbiomes.

BACKGROUND: The resistome, the collection of antibiotic resistance genes (ARGs) in a microbiome, is increasingly recognised as relevant to the development of clinically relevant antibiotic resistance. Many metagenomic studies have reported resistome differences between groups, often in connection with disease and/or antibiotic treatment. However, the consistency of resistome associations with antibiotic- and non-antibiotic-treated diseases has not been established. In this study, we re-analysed human gut microbiome data from 26 case-control studies to assess the link between disease and the resistome. RESULTS: The human gut resistome is highly variable between individuals both within and between studies, but may also vary significantly between case and control groups even in the absence of large taxonomic differences. We found that for diseases commonly treated with antibiotics, namely cystic fibrosis and diarrhoea, patient microbiomes had significantly elevated ARG abundances compared to controls. Disease-associated resistome expansion was found even when ARG abundance was high in controls, suggesting ongoing and additive ARG acquisition in disease-associated strains. We also found a trend for increased ARG abundance in cases from some studies on diseases that are not treated with antibiotics, such as colorectal cancer. CONCLUSIONS: Diseases commonly treated with antibiotics are associated with expanded gut resistomes, suggesting that historical exposure to antibiotics has exerted considerable selective pressure for ARG acquisition in disease-associated strains. Video Abstract.

Transcriptomics in serum and culture medium reveal shared and differential gene regulation in pathogenic and commensal Streptococcus suis.

Streptococcus suis colonizes the upper respiratory tract of healthy pigs at high abundance but can also cause opportunistic respiratory and systemic disease. Disease-associated S. suis reference strains are well studied, but less is known about commensal lineages. It is not known what mechanisms enable some S. suis lineages to cause disease while others persist as commensal colonizers, or to what extent gene expression in disease-associated and commensal lineages diverge. In this study we compared the transcriptomes of 21 S. suis strains grown in active porcine serum and Todd-Hewitt yeast broth. These strains included both commensal and pathogenic strains, including several strains of sequence type (ST) 1, which is responsible for most cases of human disease and is considered to be the most pathogenic S. suis lineage. We sampled the strains during their exponential growth phase and mapped RNA sequencing reads to the corresponding strain genomes. We found that the transcriptomes of pathogenic and commensal strains with large genomic divergence were unexpectedly conserved when grown in active porcine serum, but that regulation and expression of key pathways varied. Notably, we observed strong variation of expression across media of genes involved in capsule production in pathogens, and of the agmatine deiminase system in commensals. ST1 strains displayed large differences in gene expression between the two media compared to strains from other clades. Their capacity to regulate gene expression across different environmental conditions may be key to their success as zoonotic pathogens.

Environmental and maternal factors shaping tonsillar microbiota development in piglets.

BACKGROUND: The palatine tonsils are part of the mucosal immune system and stimulate immune responses through M cell uptake sampling of antigens and bacteria in the tonsillar crypts. Little is known about the development of the tonsillar microbiota and the factors determining the establishment and proliferation of disease-associated bacteria such as Streptococcus suis. In this study, we assessed tonsillar microbiota development in piglets during the first 5 weeks of life and identified the relative importance of maternal and environmental farm parameters influencing the tonsillar microbiota at different ages. Additionally, we studied the effect sow vaccination with a bacterin against S. suis on microbiota development and S. suis colonisation in their offspring. RESULTS: Amplicon sequencing of the 16S rRNA gene V3-V4 region revealed that a diverse tonsillar microbiota is established shortly after birth, which then gradually changes during the first 5 weeks of life without a large impact of weaning on composition or diversity. We found a strong litter effect, with siblings sharing a more similar microbiota compared to non-sibling piglets. Co-housing in rooms, within which litters were housed in separate pens, also had a large impact on microbiota composition. Sow parity and prepartum S. suis bacterin vaccination of sows had weaker but significant associations with microbiota composition, impacting on the abundance of Streptococcus species before and after weaning. Sex and birthweight had limited impact on the tonsillar microbiota, and none of the measured factors had consistent associations with microbiota diversity. CONCLUSIONS: The piglet tonsillar microbiota is established shortly after birth. While microbiota development is associated with both environmental and maternal parameters, weaning has limited impact on microbiota composition. Intramuscular vaccination of sows pre-partum had a significant effect on the tonsillar microbiota composition of their piglets. These findings provide new insights into the mechanisms shaping the tonsillar microbiota.