The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma.

The gut microbiome influences cancer development and the efficacy and safety of chemotherapy but little is known about its effects on lymphoma. We obtained stool samples from treatment-naive, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing on additional samples (n = 106). We compared the microbiome data from these patients with data from healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < .001), and the microbial composition differed significantly between the groups (P < .001). The abundance of the Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P < .001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = .007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = .035) and interferon gamma (P = .045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.

Gordonibacter faecis sp. nov., producing urolithin C from ellagic acid, isolated from feces of healthy Korean subjects.

A Gram-stain-positive, anaerobic, motile, and short rod-shaped bacterium, designated KGMB12511T, was isolated from the feces of healthy Koreansubjects. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KGMB12511T was closely related to Gordonibacter pamelaeae 7-10-1-bT (95.2%). The draft genome of KGMB12511T comprised 33 contigs and 2,744 protein-coding genes. The DNA G + C content was 59.9% based on whole-genome sequences. The major cellular fatty acids (>10%) of strain KGMB12511T were C18:1 cis9, C18:1 cis9 DMA (dimethylacetal), and C16:0 DMA. The predominant polar lipids included a diphosphatydilglycerol, four glycolipids, and an unidentified phospholipid. The major respiratory quinones were menaquinone 6 (MK-6) and monomethylmenaquinone 6 (MMK-6). Furthermore, HPLC analysis demonstrated the ability of strain KGMB12511T to convert ellagic acid into urolithin. Based on a comprehensive analysis of phenotypic, chemotaxonomic, and phylogenetic data, strain KGMB12511T represents a novel species in the genus Gordonibacter. The type strain is KGMB12511T (= KCTC 25343T = NBRC 116190T).

Phocaeicola acetigenes sp. nov., producing acetic acid and iso-butyric acid, isolated faeces from a healthy human.

An obligately anaerobic, non-motile, Gram-stain-negative, and rod-shaped strain KGMB11183T was isolated from the feces of healthy Koreans. The growth of strain KGMB11183T occurred at 30-45 °C (optimum 37 °C), at pH 6-9 (optimum pH 7), and in the presence of 0-0.5% NaCl (optimum 0%). Strain KGMB11183T showed 16S rRNA gene sequence similarities of 95.4% and 94.2% to the closest recognized species, Phocaeicola plebeius M12T, and Phocaeicola faecicola AGMB03916T. Phylogenetic analysis showed that strain KGMB11183T is a member of the genus Phocaeiocla. The major end products of fermentation are acetic acid and isobutyric acid. The major cellular fatty acids (> 10%) of this isolate were C18:1 cis 9, anteiso-C15:0, and summed feature 11 (iso-C17:0 3-OH and/or C18:2 DMA). The assembled draft genome sequences of strain KGMB11183T consisted of 3,215,271 bp with a DNA G + C content of 41.4%. According to genomic analysis, strain KGMB11183T has a number of genes that produce acetic acid. The genome of strain KGMB11183T encoded the starch utilization system (Sus) operon, SusCDEF suggesting that strain uses many complex polysaccharides that cannot be digested by humans. Based on the physiological, chemotaxonomic, phenotypic, and phylogenetic data, strain KGMB11183T is regarded a novel species of the genus Phocaeicola. The type strain is KGMB11183T (= KCTC 25284T = JCM 35696T).

Dietary quality and the gut microbiome in early-stage Parkinson's disease patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition. METHODS: This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences. RESULTS: Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls. CONCLUSIONS: Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed.

Bacteroides humanifaecis sp. nov., isolated from faeces of healthy Korean.

Two obligately anaerobic, Gram-stain-negative, non-motile, non-spore-forming and short rod shaped bacteria, designated KGMB07931T and KGMB10229, were isolated from faeces of two Korean persons. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains KGMB07931T and KGMB10229 were very similar to each other (99.9%) and grouped within the genus Bacteroides, displaying the highest similarity with Bacteroides uniformis ATCC 8492T (97.5%), Bacteroides rodentium JCM 16496T (96.6%), and Bacteroides fluxus YIT 12057T (94.5%). Both strains grew optimally at 37 °C and pH 7.5 in the presence of 0.5% (w/v) NaCl. The complete genome of KGMB07931T comprises 3,335 protein-coding genes with a total of 4,240,638 bp and an average G + C content of 46.3 mol%. The major fatty acids were C18:1 cis9, anteiso-C15:0, iso-C15:0, and Summed Feature 11 (iso-C17:0 3OH and/or C18:2 DMA); the predominant respiratory quinones were MK-9 and MK-10; the major fermentation end products were acetate and isobutyrate. The genome of strain KGMB07931T encoded the starch utilization system (Sus) operon, susABCDEFG, suggesting that this strain uses many complex polysaccharides that cannot be digested by humans. Based on polyphasic taxonomic data, strains KGMB07931T and KGMB10229 represent a novel species within the genus Bacteroides, for which the name Bacteroides humanifaecis sp. nov. is proposed. The type strain is KGMB07931T (= KCTC 25160T = NBRC 115005T).

Collinsella acetigenes sp. nov., an Anaerobic Actinobacterium Isolated from Human Feces, and Emended Description of the Genus Collinsella and Collinsella aerofaciens.

A novel actinobacterial strain, Gram-positive, anaerobic, non-motile, and rod-shaped, designated KGMB02528T, was isolated from healthy human feces. Cells of strain KGMB02528T grew optimally at pH 7.0 and 37 °C and in the presence of 0% (w/v) NaCl. Based on 16S rRNA gene sequence similarity, strain KGMB04489T belonged to the genus Collinsella and was most closely related to Collinsella aerofaciens DSM 17552T (95.8%). The DNA G + C content was 58.0 mol%. The major cellular fatty acids (> 10%) were C16:0 DMA, C16:0 ALDE, C14:0 DMA, and C12:0. The predominant end product of fermentation was acetic acid. The cell wall peptidoglycan of strain KGMB02528T contained alanine, glutamic acid, and lysine, while diaminopimelic acid was not detected. The polar lipids were composed of two unidentified phospholipids and unidentified nine glycolipids. Based on the phenotypic, chemotaxonomic, and phylogenetic properties, strain KGMB02528T represents a novel species of the genus Collinsella, for which the name Collinsella acetigenes sp. nov. is proposed. The type strain is Collinsella acetigenes KGMB02528T (= KCTC 15847T = CCUG 73987T). The description of the genus Collinsella is emended to accommodate the new species.The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of Collinsella acetigenes KGMB02528T is MT117838. The whole-genome shotgun BioProject number is PRJNA623694 with the accession number JABBCP000000000.

Senegalimassilia faecalis sp. nov., an anaerobic actinobacterium isolated from human faeces, and emended description of the genus Senegalimassilia.

A novel actinobacterial strain, designated KGMB04484T, was isolated from healthy human faeces sampled in the Republic of Korea. Cells of strain KGMB04484T were strictly anaerobic, Gram-stain-positive, catalase-positive, oxidase-negative, non-motile coccobacilli and formed tiny colonies on Columbia agar with 5 % horse blood. On the basis of 16S rRNA gene sequence similarity, strain KGMB04484T was affiliated with the genus Senegalimassilia in the family Coriobacteriaceae and its closest relative was Senegalimassilia anaerobia JC110T (96.28 % sequence similarity). The DNA G+C content of strain KGMB04484T was 61.2 mol%. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid, an unidentified aminolipid and three unidentified glycolipids. The predominant cellular fatty acids (>10 %) of strain KGMB04484T were C14 : 0, C16 : 0 and C16 : 0 dimethyl acetal. Based on its phylogenetic, physiological and chemotaxonomic characteristics, strain KGMB04484T is considered to represent a novel species within the genus Senegalimassilia, for which the name Senegalimassilia faecalis sp. nov. is proposed. The type strain is KGMB04484T (=KCTC 15721T=CCUG 72347T).

Replication of Vibrio cholerae classical CTX phage.

The toxigenic classical and El Tor biotype Vibrio cholerae serogroup O1 strains are generated by lysogenization of host-type-specific cholera toxin phages (CTX phages). Experimental evidence of the replication and transmission of an El Tor biotype-specific CTX phage, CTX-1, has explained the evolution of V. cholerae El Tor biotype strains. The generation of classical biotype strains has not been demonstrated in the laboratory, and the classical biotype-specific CTX phage, CTX-cla, is considered to be defective with regard to replication. However, the identification of atypical El Tor strains that contain CTX-cla-like phage, CTX-2, indicates that CTX-cla and CTX-2 replicate and can be transmitted to V. cholerae strains. The replication of CTX-cla and CTX-2 phages and the transduction of El Tor biotype strains by various CTX phages under laboratory conditions are demonstrated in this report. We have established a plasmid-based CTX phage replication system that supports the replication of CTX-1, CTX-cla, CTX-2, and CTX-O139. The replication of CTX-2 from the tandem repeat of lysogenic CTX-2 in Wave 2 El Tor strains is also presented. El Tor biotype strains can be transduced by CTX phages in vitro by introducing a point mutation in toxT, the transcriptional activator of the tcp (toxin coregulated pilus) gene cluster and the cholera toxin gene. This mutation also increases the expression of cholera toxin in El Tor strains in a sample single-phase culture. Our results thus constitute experimental evidence of the genetic mechanism of the evolution of V. cholerae.

Evidence for several waves of global transmission in the seventh cholera pandemic.

Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.

Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer.

BACKGROUND AND OBJECTIVES: Metastatic colon cancer patients are treated with the chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot predict the response of chemotherapeutic agent, so it is necessary to find which regimen is adequate before starting chemotherapy. METHODS: Enrolled patients are randomized into either conventional treatment or planned treatment preceded by pretreatment genetic analysis. Blood samples of patients in planned treatment group (N = 53) were analyzed for the genetic polymorphism before selection of chemotherapeutic agents. Target genes were XPD-751, GSTP-1-105, XRCC1-399 for oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed tomographic scan after completion of three cycles of chemotherapy. RESULTS: Overall response rate was significantly higher in planned group (67.9% vs. 46.3%, P = 0.020). In FOLFOX group, response rate was significantly improved in the planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference didn't reach statistical significance (50% vs. 42.5%, P = 0.776). CONCLUSIONS: We found significantly improved response rates in the chemotherapy of metastatic colon cancer by pretreatment genetic analysis, especially in FOLFOX group.

Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice.

IMPORTANCE: The human gut microbiome mediates bidirectional interaction within the gut-liver axis, while liver diseases, including liver cirrhosis, are very closely related to the state of the gut environment. Thus, improving the health of the gut-liver axis by targeting the intestinal microbiota is a potential therapeutic approach in hepatic diseases. This study examines changes in metabolomics and microbiome composition by treating bacteria derived from the human gut in mice with liver cirrhosis. Interorgan-based multiomics profiling coupled with functional examination demonstrated that the treatment of Bacteroides dorei pertained to protective effects on liver cirrhosis by normalizing the functional, metabolic, and metagenomic environment through the gut-liver axis. The study provides the potential value of a multiomics-based and interorgan-targeted evaluation platform for the comprehensive examination and mechanistic understanding of a wide range of biologics, including gut microbes. Furthermore, the current finding also suggests in-depth future research focusing on the discovery and validation of next-generation probiotics and products (postbiotics).

Draft genome sequence of Weissella koreensis KCTC 3621T.

Weissella koreensis is a Gram-positive, rod-shaped, nonmotile, and facultative anaerobic species belonging to the lactic acid bacteria (LAB). The members of this species have been repeatedly isolated from kimchi (a traditional Korean fermented food) and are known for their beneficial effects on human and animal intestinal microflora through producing various clinically important amino acids such as γ-aminobutyric acid and ornithine. Here we report the genome sequence of the type strain of W. koreensis (KCTC 3621(T)) to provide taxonomic and functional insights into the species.

Draft genome sequence of Klebsiella pneumoniae subsp. pneumoniae DSM 30104T.

Klebsiella pneumoniae is a Gram-negative, rod-shaped, nonmotile, and opportunistic pathogenic species with clinical importance. It is a part of natural flora of humans and animals. Here we report the draft genome sequence of the type strain of Klebsiella pneumoniae subsp. pneumoniae (DSM 30104(T)) to provide taxonomic and functional insights into the species.

Genome sequence of Lactobacillus mucosae LM1, isolated from piglet feces.

Lactobacillus mucosae LM1, isolated from stool samples of a healthy piglet, displays good in vitro mucin adhesion and antimicrobial activity against pathogenic bacteria. To elucidate its antimicrobial effects and to find its epithelial cell and mucin adhesion genes, the genomic sequence of L. mucosae LM1 was investigated.

Complete genome sequence of Mycobacterium intracellulare clinical strain MOTT-36Y, belonging to the INT5 genotype.

Here we report the complete genome sequence of the Mycobacterium intracellulare clinical strain MOTT-36Y, previously grouped into the INT5 genotype among the 5 genotypes of M. intracellulare. This genome sequence will serve as a valuable reference for understanding the disparity in virulence and epidemiologic traits between M. intracellulare-related strains.

Complete genome sequence of Mycobacterium intracellulare strain ATCC 13950(T).

Here we report the first complete genome sequence of Mycobacterium intracellulare ATCC 13950(T), a Mycobacterium avium complex (MAC) strain. This genome sequence will serve as a valuable reference for understanding the epidemiologic, biological, and pathogenic aspects of the disparity between MAC members.

Complete genome sequence of Mycobacterium intracellulare clinical strain MOTT-02.

Here, we report the first complete genome sequence of the Mycobacterium intracellulare clinical strain MOTT-02, which was previously grouped in the INT2 genotype of M. intracellulare. This genome sequence will serve as a valuable reference for improving the understanding of the disparity in the virulence and epidemiologic traits between M. intracellulare genotypes.

Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae.

Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the sixth and the current seventh pandemics, respectively. Cholera researchers continually face newly emerging and reemerging pathogenic clones carrying diverse combinations of phenotypic and genotypic properties, which significantly hampered control of the disease. To elucidate evolutionary mechanisms governing genetic diversity of pandemic V. cholerae, we compared the genome sequences of 23 V. cholerae strains isolated from a variety of sources over the past 98 years. The genome-based phylogeny revealed 12 distinct V. cholerae lineages, of which one comprises both O1 classical and El Tor biotypes. All seventh pandemic clones share nearly identical gene content. Using analogy to influenza virology, we define the transition from sixth to seventh pandemic strains as a "shift" between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages. In contrast, transition among clones during the present pandemic period is characterized as a "drift" between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V. cholerae O139 and V. cholerae O1 El Tor hybrid clones. Based on the comparative genomics it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones.

Oral and gut dysbiosis leads to functional alterations in Parkinson's disease.

Although several studies have identified a distinct gut microbial composition in Parkinson's disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P < 0.038). Functional analysis revealed that microbial gene markers for glutamate and arginine biosynthesis were downregulated, while antimicrobial resistance gene markers were upregulated in PD patients than healthy controls (all P < 0.001). We identified a connection between the oral and gut microbiota in PD, which might lead to functional alteration of the microbiome in PD.

Genome sequence of Lactobacillus johnsonii PF01, isolated from piglet feces.

Lactobacillus johnsonii PF01, an autochthonous bacterium of the gastrointestinal tract, was isolated from a fecal sample from a piglet. The strain adhered specifically to the duodenal and jejunal epithelial cells of the piglet and had high bile resistance activity. Here we report the genomic sequence of L. johnsonii PF01.