Guangwen Luo

Comorbidities are prevalent in digestive cancers, intensifying patient discomfort and complicating prognosis. Identifying potential comorbidities and investigating their genetic connections in a systemic manner prove to be instrumental in averting additional health challenges during digestive cancer management. Here, we investigated 150 diseases across 18 categories by collecting and integrating various factors related to disease comorbidity, such as disease-associated SNPs or genes from sources like MalaCards, GWAS Catalog and UK Biobank. Through this extensive analysis, we have established an integrated pleiotropic gene set comprising 548 genes in total. Particularly, there enclosed the genes encoding major histocompatibility complex or related to antigen presentation. Additionally, we have unveiled patterns in protein-protein interactions and key hub genes/proteins including TP53, KRAS, CTNNB1 and PIK3CA, which may elucidate the co-occurrence of digestive cancers with certain diseases. These findings provide valuable insights into the molecular origins of comorbidity, offering potential avenues for patient stratification and the development of targeted therapies in clinical trials.

A Gram-staining-negative, non-spore-forming, short, straight rod, non-motile, and obligate anaerobic bacterial strain, AF73-05CM02^T, was isolated from a fecal sample of a 30 years old healthy male living in Shenzhen, China. Colonies were approximately 0.2 mm in diameter, beige, and circular after 4 days of incubation on PYG agar under anaerobic conditions at 37°C. Strain AF73-05CM02^T grew in a temperature range between 30 and 42°C and a pH range from 6.0 to 8.5, with optimum growth at 37–42°C and pH 7.0. 16S rRNA gene sequence analysis demonstrated that strain AF73-05CM02^T belongs to the genus Christensenella and showed the highest level of sequence similarity (98.68%) with Christensenella minuta DSM 22607^T. The predominant fatty acids of strain AF73-05CM02^T were C_10:0 (7.5%), iso-C_11:0 (5.6%), C_12:0 (7.2%), C_14:0 (46.6%), iso-C_15:0 (7.4%), C_16:0 (9.7%), and C_18:1 ω9c (6.9%). Acetic acid, formic acid, butyric acid, and lactic acid were the end products of glucose fermentation. The strain was negative for catalase, indole production, and hydrolysis of gelatin. Genomic relatedness analyses based on average nucleotide identity (ANI) indicated that strain AF73-05CM02^T significantly differed from other species of the genus Christensenella, showing ANI values less than 82.89% with the phylogenetically closest species. The G + C content of the genomic DNA was 52.07 mol% from the genome sequence, which differs from that of Christensenella minuta. Several physiological, biochemical, and genotypic properties differentiated the novel bacterial strain from the related species, indicating that the strain represents a new species of the genus Christensenella for which the name Christensenella intestinihominis sp. nov. is proposed, with strain AF73-05CM02^T ( = CGMCC 1.5207^T = DSM 103477^T ) being the type strain. The following study explored the cholesterol-lowering function of strains AF73-05CM02^T and Christensenella minuta DSM 22067^T and revealed that the two strains exhibit the capacity for removing cholesterol with efficiency rates of 36.6 and 54.3% and produce exopolysaccharide of 234 and 271 mg/L, respectively.

Modulating gut microbiota to promote host health is well recognized. Therefore, people consume dietary products containing traditional probiotics in wishing to improve their health, and they need more research-based advices on how to select products with suitable probiotic species. Probiotic designers are sometimes confused about how to design precision products for different consumers by taking advantages of different probiotic species’ strengths. Additionally, large-scale analyses on traditional probiotic complementarity potentials and their roles in gut microbiome related to common diseases are not well understood. Here, we comprehensively analyzed 444 genomes of major traditional probiotic (sub) species (MTPS, n = 15) by combining one newly sequenced genome with all of the public NCBI-available MTPS-related genomes. The public human fecal metagenomic data (n = 1,815) of eight cohorts were used to evaluate the roles of MTPS, compared to other main gut bacteria, in disease association by examining the species enrichment direction in disease group or the control group. Our work provided a comprehensive genetic landscape and complementarity relations for MTPS and shed light on personalized probiotic supplements for consumers with different health status and the necessity that researchers and manufactures could explore novel probiotics as well as traditional ones.

Butyrate-producing bacteria can biosynthesize butyrate and alleviate inflammatory diseases. However, few studies have reported that the genus Collinsella has the ability to produce butyric acid. Here, our study depicts a Collinsella strain, which is a rod-shaped obligate anaerobe that is able to produce butyric acid. This microorganism was isolated from a human gut, and the optimal growth conditions were found to be 37 °C on PYG medium with pH 6.5. The 16S rRNA gene sequence demonstrated that this microorganism shared 99.93% similarity with C. aerofaciens ATCC 25986^T, which was higher than the threshold (98.65%) for differentiating two species. Digital DNA–DNA hybridization and average nucleotide identity values also supported that this microorganism belonged to the species C. aerofaciens. Distinct phenotypic characteristics between TF06-26 and the type strain of C. aerofaciens, such as the fermentation of D-lactose, D-fructose and D-maltose, positive growth under pH 5 and 0.2% (w/v) cholate, suggested this strain was a novel subspecies. Comparative genome analysis revealed that butyric acid kinase and phosphate butyryltransferase enzymes were coded exclusively by this strain, indicating a specific butyric acid-producing function of this C. aerofaciens subspecies within the genus Collinsella. Thus, Collinsella aerofaciens subsp. shenzhenensis subsp. nov. was proposed, with set strain TF06-26^T (=CGMCC 1.5216^T = DSM 105138^T) as the type strain.

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes.

This study investigated the effects of KLDS 1.8701 and AD1 administrations by gavage on intestinal microflora and mucosal immunity in diarrhea mice infected by Escherichia coli O157:H7 compared to normal mice. The levels of E. coli, Enterobacteria, and Enterococcus decreased significantly (P < 0.05), while viable counts of Lactobacilli and Bifidobacterium increased in diarrhea mice. Moreover, KLDS 1.8701 and AD1 improved secretion of secretory immunoglobulin A and enhanced the levels of interferon-γ and interleukin. Results indicate that KLDS 1.8701 and AD1 could effectively alleviate diarrhea in mice via modulation of intestinal microflora and improve the function of immune system. The study on the effect of KLDS1.8701 and AD1 supplementation in human flora-associated animal models was recommended.

Lactobacillus helveticus, an obligatory hetero-fermentative LAB, is Generally Recognized as Safe (GRAS) and is gaining popularity for application in dairy products. Lactic acid bacteria (LAB) play a remarkable role in inhibiting the growth of pathogenic bacteria in food products, without disturbing the sensory attributes of the food. In this study, the screening of the antimicrobial potential of Lactobacillus helveticus KLDS 1.8701 against four food-borne pathogens including Listeria monocytogenes ATCC 19115, Salmonella typhimurium ATCC 14028, Staphylococcus aureus ATCC 25923, and Escherichia coli O157:H7 ATCC 43889 in vitro was inspected using the Oxford cup method and mixed culture inhibition assays. The organic acid production and antimicrobial potential of the cell-free supernatants (CFS) have been evaluated via different treatments and analysis using high performance liquid chromatography (HPLC). The analysis results revealed that KLDS 1.8701 exhibited the highest antimicrobial potential compared to other antimicrobial strains. The antimicrobial activity of KLDS 1.8701 resulted from the organic acids in the culture and CFS. From the study, it was found that carbon sources, as well as organic acid production, accelerate the antimicrobial activity of KLDS 1.8701 and the fructooligosaccharides (FOS) were considered the best for improving the proliferation of KLDS 1.8701 and supporting its antimicrobial action. Results of the mixed culture inhibition assays showed that part of the antimicrobial activity resulted from the inhibitory action of the bacteria itself in culture, and this action required cellular contact between the food-borne pathogens and KLDS 1.8701. Conversely, the results of the antimicrobial spectrum assay revealed that some Lactobacilli remained unaffected by KLDS 1.8701. KLDS 1.8701 might also be favorable for use as a supplementary starter in fermented dairy productions. Furthermore, KLDS 1.8701 could survive well under GI tract conditions. Further studies on in vivo inhibition assays and the probiotic effects are recommended.