Background: Probiotics have been used to regulate the gut microbiota and physiology in various contexts, but their precise mechanisms of action remain unclear.Results: By population genomic analysis of 418Bifidobacterium longumstrains, including 143 newly sequenced in this study, three geographically distinct gene pools/populations, BLAsia1, BLAsia2, and BLothers, were identified. Genes involved in cell wall biosynthesis, particularly peptidoglycan biosynthesis, varied considerably among the core genomes of the different populations, but accessory genes that contributed to the carbohydrate metabolism were significantly distinct. Although active transmission was observed inter-host, inter-country, inter-city, intra-community, and intra-family, a singleB. longumclone seemed to reside within each individual. A significant negative association was observed between host age and relative abundance ofB. longum, while there was a strong positive association between host age and strain genotype [e.g., single nucleotide polymorphisms in the arginine biosynthesis pathway]. Further animal experiments performed with theB. longumisolates via using ad-galactose-induced aging mouse model supported these associations, in whichB. longumstrains with different genotypes in arginine biosynthesis pathway showed divergent abilities on protecting against host aging possibly via their different abilities to modify the metabolism of gut microbes.Conclusions: This is the first known example of research on the evolutionary history and transmission of this probiotic species. Our results propose a new mechanistic insight for promoting host longevity via the informed use of specific probiotics or molecules.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (−44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.

Non-toxigenic Vibrio cholerae isolates have been found associated with diarrheal disease globally, however, the global picture of non-toxigenic infections is largely unknown. Among non-toxigenic V. cholerae, ctxAB negative, tcpA positive (CNTP) isolates have the highest risk of disease. From 2001 to 2012, 71 infectious diarrhea cases were reported in Hangzhou, China, caused by CNTP serogroup O1 isolates. We sequenced 119 V. cholerae genomes isolated from patients, carriers and the environment in Hangzhou between 2001 and 2012, and compared them with 850 publicly available global isolates. We found that CNTP isolates from Hangzhou belonged to two distinctive lineages, named L3b and L9. Both lineages caused disease over a long time period with usually mild or moderate clinical symptoms. Within Hangzhou, the spread route of the L3b lineage was apparently from rural to urban areas, with aquatic food products being the most likely medium. Both lineages had been previously reported as causing local endemic disease in Latin America, but here we show that global spread of them has occurred, with the most likely origin of L3b lineage being in Central Asia. The L3b lineage has spread to China on at least three occasions. Other spread events, including from China to Thailand and to Latin America were also observed. We fill the missing links in the global spread of the two non-toxigenic serogroup O1 V. cholerae lineages that can cause human infection. The results are important for the design of future disease control strategies: surveillance of V. cholerae should not be limited to ctxAB positive strains. Non-toxigenic Vibrio cholerae isolates are associated with diarrheal disease globally. Among them, ctxAB negative, tcpA positive (CNTP) isolates have the highest risk of disease because they may be able to colonize the human intestine. By population genomic analysis of 850 previously published genomes and 119 newly sequenced genomes in this study, we found that most of CNTP isolates can be attributed into two distinctive lineages, L3b and L9. Both lineages are not only circulating in local regions causing endemic disease, but have been spreading worldwide over the past 100 years. Central Asia is the most likely origin of the L3b lineage, and the strains spread to China on at least three occasions. The L3b strains were also exported from China to other parts of the world, and one of the migrations are related to the groups that circulated in Latin America. Within Hangzhou, a modernized city in China, aquatic food products are the most likely medium of CNTP strains, and a spread pattern from rural aquafarms to the urban areas was observed. This work filled the missing links in the global spread of two non-toxigenic serogroup O1 V. cholerae lineages that can cause human infection. The results suggest that in future disease control efforts, the sampling of V. cholerae should not be limited to the apparently toxic isolates, and that a more thorough and unbiased sampling framework is needed.

Significance: Over the last few years, there has been a great deal of scientific debate regarding whether the plague bacterium,Yersinia pestis, spread from a Western European reservoir during the second plague pandemic, or if it repeatedly came to Europe from Asia. Here, we make a synthesis of the available evidence, including genomes of ancient DNA and historical, archeological, and ecological information. We conclude that the bacterium most likely came to Europe from Asia several times during the second plague pandemic.

Vibrio fluvialis is a food-borne pathogen with epidemic potential that causes cholera-like acute gastroenteritis and sometimes extraintestinal infections in humans. However, research on its genetic diversity and pathogenicity-related genetic elements based on whole genome sequences is lacking. In this study, we collected and sequenced 130 strains of V. fluvialis from 14 provinces of China, and also determined the susceptibility of 35 of the strains to 30 different antibiotics. Combined with 52 publicly available V. fluvialis genomes, we inferred the population structure and investigated the characteristics of pathogenicity-related factors. The V. fluvialis strains exhibited high levels of homologous recombination and were assigned to two major populations, VflPop1 and VflPop2, according to the different compositions of their gene pools. VflPop2 was subdivided into groups 2.1 and 2.2. Except for VflPop2.2, which consisted only of Asian strains, the strains in VflPop1 and VflPop2.1 were distributed in the Americas, Asia and Europe. Analysis of the pathogenicity potential of V. fluvialis showed that most of the identified virulence-related genes or gene clusters showed high prevalence in V. fluvialis , except for three mobile genetic elements: pBD146, ICEVflInd1 and MGIVflInd1, which were scattered in only a few strains. A total of 21 antimicrobial resistance genes were identified in the genomes of the 182 strains analysed in this study, and 19 (90%) of them were exclusively present in VflPop2. Notably, the tetracycline resistance-related gene tet(35) was present in 150 (95%) of the strains in VflPop2, and in only one (4%) strain in VflPop1, indicating it was population-specific. In total, 91% of the 35 selected strains showed resistance to cefazolin, indicating V. fluvialis has a high resistance rate to cefazolin. Among the 15 genomes that carried the previously reported drug resistance-related plasmid pBD146, 11 (73%) showed resistance to trimethoprim-sulfamethoxazole, which we inferred was related to the presence of the dfr6 gene in the plasmid. On the basis of the population genomics analysis, the genetic diversity, population structure and distribution of pathogenicity-related factors of V. fluvialis were delineated in this study. The results will provide further clues regarding the evolution and pathogenic mechanisms of V. fluvialis , and improve our knowledge for the prevention and control of this pathogen.