• Colorectal cancer
• Human gut microbiome
• Machine learning
• MicroBiomeGSM
• Taxonomic biomarkers

• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Humans
• Gastrointestinal Microbiome/genetics
• Biomarkers, Tumor/genetics
• Metagenomics/methods
• Algorithms
• Bacteria/classification
• Bacteria/genetics

• Biotherapeutics
• Gut microbiome
• Postbiotics
• Probiotics
• Psychobiotics
• Synbiotics

• Probiotics/therapeutic use
• Probiotics/pharmacology
• Humans
• Gastrointestinal Microbiome/drug effects
• Animals

• Gut–lung axis
• Immune system
• Lung cancer
• Probiotics

• Probiotics/therapeutic use
• Humans
• Lung Neoplasms/therapy
• Prognosis
• Gastrointestinal Microbiome
• Randomized Controlled Trials as Topic

• Inflammation associated carcinogenesis
• KCNK6
• METTL3
• YTHDF2
• lactylation

• Animals
• Humans
• Mice
• Colitis/metabolism
• Colitis/chemically induced
• Homeostasis
• Methyltransferases/metabolism
• Methyltransferases/genetics
• Carcinogenesis
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Histones/metabolism
• Inflammation/metabolism
• Colonic Neoplasms/etiology
• Colonic Neoplasms/metabolism
• Colonic Neoplasms/pathology
• Dextran Sulfate
• Mice, Knockout
• Colon/pathology
• Colon/metabolism
• Colon/immunology
• Disease Models, Animal
• Caco-2 Cells
• HCT116 Cells
• Macrophages/metabolism
• Macrophages/immunology
• Azoxymethane/toxicity
• Mice, Inbred C57BL

• colorectal cancer
• epidemiology
• molecular pathogenesis
• risk factor
• therapeutic strategy

• Humans
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/genetics
• Carcinogenesis/genetics
• Animals
• Risk Factors

• RAI-0000000251 New Brunswick (NB) Innovation Foundation
• DUO2023 Vitalité Health network of NB
• CHA-22 Canadian Cancer Society

• Food supplement
• Functional food
• Health benefit
• Microencapsulation
• Probiotic

• Griffith University

• Acne vulgaris
• atopic dermatitis
• gut microbiome
• probiotics

• Leukoplakia
• Lichen
• OPMD
• Oral cancer
• Oral microbiota

• Humans
• Lichen Planus, Oral/microbiology
• Microbiota
• Leukoplakia, Oral/microbiology
• Mouth Neoplasms/microbiology
• Dysbiosis/microbiology
• Mouth/microbiology
• Saliva/microbiology

• HPV-infection
• cervical cancer
• chemoradiotherapy
• human papillomavirus
• prebiotic
• probiotic
• synbiotic

• dermatological diseases
• gut microbiota
• inference
• mendelian randomization analysis
• therapeutics

• Humans
• Gastrointestinal Microbiome/genetics
• Genome-Wide Association Study
• Mendelian Randomization Analysis
• Acne Vulgaris
• Bacteroides/genetics

• Female
• Humans
• Prebiotics
• Genital Neoplasms, Female/prevention & control
• Probiotics/therapeutic use
• Microbiota
• Genitalia, Female

• CYP2W1
• Colon cancer
• Lacticaseibacillus rhamnosus GG
• cell-free supernatant
• hesperidin
• probiotics.

• Humans
• Lacticaseibacillus rhamnosus
• Hesperidin/pharmacology
• Caco-2 Cells
• Cell Survival
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/genetics
• Gene Expression
• Cytochrome P450 Family 2

• Colitis-associated carcinogenesis
• Gut microbiota
• IBD therapy
• Immune cells
• Intestinal epithelial cells
• Intestinal mesenchymal cells

• No. 81972607 the National Natural Science Foundation of China Program grant
• No. ZYGD20003 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
• No. 2020YJ0066 the Basic Research for Application of Sichuan Province, China

• biotechnology
• microbiology

• Humans
• Animals
• Rats
• Lactobacillales
• Caco-2 Cells
• Egypt
• Probiotics/metabolism
• Anti-Infective Agents
• Fermented Foods/microbiology
• Superoxide Dismutase

• Cairo University

• Biomaterials
• Biomedical application
• Living materials
• Organic functional substance

• Biocompatible Materials/pharmacology
• Polymers/pharmacology
• Drug Delivery Systems
• Wound Healing

• OSCC
• biomarkers
• confocal microscopy
• diagnosis
• histology
• imaging
• metabolomic
• microbiome
• optical coherence tomography
• oral carcinoma
• prognosis
• ultrasounds

• cancer microenvironment
• cancer immunotherapy
• metabolism
• microbiome

• Male
• Mice
• Female
• Animals
• Methionine/metabolism
• Hydrogen Sulfide/metabolism
• Gastrointestinal Microbiome
• Racemethionine
• Neoplasms
• Sulfur

• FI2 GM143339 NIGMS NIH HHS
• P30 ES010126 NIEHS NIH HHS
• R01 AI160774 NIAID NIH HHS
• ZIA ES102205 Intramural NIH HHS
• R35 GM143024 NIGMS NIH HHS
• R56 AG071256 NIA NIH HHS
• R01 AI123193 NIAID NIH HHS
• P42 ES031007 NIEHS NIH HHS
• R01 AG076019 NIA NIH HHS
• U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)
• U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
• UNC Superfund Research Program (P42ES031007) and Center for Environmental Health and Susceptibility (P30ES010126)
• U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)

• Application
• gut microbiota
• plant-derived polysaccharides
• prebiotic activity
• structure- activity relationship

• Prebiotics
• Gastrointestinal Microbiome/drug effects
• Humans
• Polysaccharides/pharmacology
• Intestines/microbiology
• Intestines/drug effects
• Plants/chemistry
• Dietary Fiber/pharmacology
• Animals
• Intestinal Diseases/drug therapy
• Intestinal Diseases/prevention & control

• Colorectal cancer
• Lactobacillus casei
• Mesenchymal stem cells
• Newcastle disease virus

• SCFA
• anticancer
• fiber
• folic acid
• gastrointestinal tract
• inulin
• lactobacillus
• microbiota
• pectin
• tryptophan

• Barrett’s esophagus
• DNA damage
• gastroesophageal reflux disease (GERD)
• inflammation
• probiotics
• reactive oxygen species

• to Claudia Andl University of Central Florida College of Medicine

• 2D representations
• AggMapNet
• MEGMA
• biomarker
• disease prediction
• manifold learning
• metagenomic
• multichannel
• unsupervised learning

• oncology
• biomarkers

• Humans
• Metagenome
• Early Detection of Cancer
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/genetics
• Adenocarcinoma/diagnosis
• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Prognosis
• Gastroesophageal Reflux/genetics
• Carcinogenesis
• Escherichia coli
• Biomarkers

• R01 CA202797 NCI NIH HHS
• R01 CA184792 NCI NIH HHS
• R01 CA181572 NCI NIH HHS
• R01 CA072851 NCI NIH HHS
• R01 CA227602 NCI NIH HHS
• Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)

Melanoma is a malignant tumor with a high mortality rate. Some microorganisms have been shown to activate the immune system and limit cancer progression. The objective of this study is to evaluate the anti-melanoma effect of Neospora caninum, a livestock pathogen with no pathogenic activity in humans.

Neospora caninum tachyzoites were inoculated into a C57BL/6 mouse melanoma model by intratumoral and distal subcutaneous injections. Tumor volumes were measured, and cell death areas were visualized by hematoxylin and eosin staining and quantified. Apoptosis in cell cultures and whole tumors was detected by propidium iodide (PI) and TUNEL staining, respectively. Cytokine and tumor-associated factor levels in tumors and spleens were detected by real-time quantitative polymerase chain reaction. Infiltration of macrophages and CD8⁺ T cells in the tumor microenvironment (TME) were detected by immunohistochemistry with anti-CD68 and anti-CD8 antibodies, respectively. Finally, 16S rRNA sequencing of mice cecal contents was performed to evaluate the effect of N. caninum on gut microbial diversity.

Intratumoral and distal subcutaneous injections of N. caninum resulted in significant inhibition of tumor growth (P < 0.001), and more than 50% of tumor cells were dead without signs of apoptosis. Neospora caninum treatment significantly increased the mRNA expression levels of IL-12, IFN-γ, IL-2, IL-10, TNF-α, and PD-L1 in the TME, and IL-12 and IFN-γ in the spleen of tumor-bearing mice (P < 0.05). An increase in the infiltration of CD8⁺ T cells and macrophages in the TME was observed with these cytokine changes. Neospora caninum also restored the abundance of gut microbiota Lactobacillus, Lachnospiraceae, Adlercreutzia, and Prevotellaceae associated with tumor growth, but the changes were not significant.

Neospora caninum inhibits B16F10 melanoma by activating potent immune responses and directly destroying the cancer cells. The stable, non-toxic, and efficacious properties of N. caninum demonstrate the potential for its use as a cancer treatment.

The online version contains supplementary material available at 10.1186/s13071-022-05456-8.

• B16F10 melanoma
• Cell death
• Gut microbiota
• Neospora caninum
• Th1 immunity

Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.

• colorectal cancer
• gut micro-organisms
• immune cell
• intestinal inflammation
• intestinal microecology
• microbial-associated molecular patterns
• pattern recognition receptors
• probiotics
• toll-like receptors

A complex balanced equilibrium of the bacterial ecosystems exists in the oral cavity that can be altered by tobacco smoking, psychological stressors, bad dietary habit, and chronic periodontitis. Oral dysbiosis can promote the onset and progression of oral squamous cell carcinoma (OSCC) through the release of toxins and bacterial metabolites, stimulating local and systemic inflammation, and altering the host immune response. During the process of carcinogenesis, the composition of the bacterial community changes qualitatively and quantitatively. Bacterial profiles are characterized by targeted sequencing of the 16S rRNA gene in tissue and saliva samples in patients with OSCC. Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis, Fusobacterium periodonticum, Prevotella tannerae, and Prevotella intermedia are the significantly increased bacteria in salivary samples. These have a potential diagnostic application to predict oral cancer through noninvasive salivary screenings. Oral lactic acid bacteria, which are commonly used as probiotic therapy against various disorders, are valuable adjuvants to improve the response to OSCC therapy.

• Bacteria/genetics
• Carcinoma, Squamous Cell/etiology
• Humans
• Microbiota/genetics
• Mouth Neoplasms/etiology
• Mouth Neoplasms/genetics
• RNA, Ribosomal, 16S/genetics

Probiotics are bacterial strains that are known to provide host health benefits. Limosilactobacillus reuteri is a well-documented lactic acid bacterium that has been cultured from numerous human sites. The strain investigated was L. reuteri DSM 20016, which has been found to produce useful metabolites. The strain was explored using genomic and proteomic tools, manual searches, and databases, including KEGG, STRING, BLAST Sequence Similarity Search, and UniProt. This study located over 200 key genes that were involved in human health benefit pathways. L. reuteri DSM 20016 has metabolic pathways to produce acetate, propionate, and lactate, and there is evidence of a pathway for butanoate production through a FASII mechanism. The bacterium produces histamine through the hdc operon, which may be able to suppress proinflammatory TNF, and the bacterium also has the ability to synthesize folate and riboflavin, although whether they are secreted is yet to be explored. The strain can bind to human Caco2 cells through srtA, mapA/cnb, msrB, and fbpA and can compete against enteric bacteria using reuterin, which is an antimicrobial that induces oxidative stress. The atlas could be used for designing metabolic engineering approaches to improve beneficial metabolite biosynthesis and better probiotic-based cures.

• Metabolism
• Microbiome
• Microbiota
• Oral cancer
• Oral cavity

• cancer
• microbiology
• medical research

• Bacteria/genetics
• Colorectal Neoplasms/diagnosis
• Dysbiosis/microbiology
• Humans
• Neoplasm Recurrence, Local
• Pilot Projects
• RNA, Ribosomal, 16S/genetics

• Lee foundation, Singapore
• National University Health System

Lactic acid bacteria (LAB) are Gram-positive bacteria which are considered for use as adjuvant therapeutics in management of various disease ailments, including obesity, irritable bowel syndrome, lactose intolerance and cancer. To investigate the possible use of Lactococcus lactis strains from our collection in treatment of gastrointestinal cancer, we tested them for the ability to arrest proliferation of human colorectal adenocarcinoma cells (Caco-2). Results of the BrdU assay showed that the anti-proliferative activity of L. lactis cells is strain-specific. We found that particularly, two strains, L. lactis IBB109 and L. lactis IBB417, exhibited the most potent inhibitory effect. Moreover, both strains triggered interleukin 18 gene expression, normally inhibited in Caco-2 (cancer) cells. To examine the probiotic potential of the two strains, we tested them for bile salts and acid tolerance, as well as adhesion properties. Both isolates exhibited probiotic potential—they survived in the presence of 0.3% bile salts and tolerated exposure to low pH and osmotic stress. Notably, we found that L. lactis IBB417 displayed better adherence to mucus and Caco-2 cells than L. lactis IBB109. Additionally, by microdilution tests we confirmed that both strains are sensitive to all nine antibiotics of human and veterinary importance listed by the European Food Safety Authority. Finally, by in silico investigations of whole genome sequencing data, we revealed the genetic features of L. lactis IBB109 and L. lactis IBB417 that can be associated with functional (e.g., adhesion and carbohydrate metabolic genes) and safety (e.g., virulence and antibiotic resistance) aspects of the strains, confirming their health-promoting potential.

Several strains of lactic acid bacteria are potent probiotics and can cure a variety of diseases using different modes of actions. These bacteria produce antimicrobial peptides, bacteriocins, which inhibit or kill generally closely related bacterial strains and other pathogenic bacteria such as Listeria, Clostridium, and Salmonella. Bacteriocins are cationic peptides that kill the target cells by pore formation and the dissipation of cytosolic contents, leading to cell death. Bacteriocins are also known to modulate native microbiota and host immunity, affecting several health-promoting functions of the host. In this review, we have discussed the ability of bacteriocin-producing probiotic lactic acid bacteria in the modulation of gut microbiota correcting dysbiosis and treatment/maintenance of a few important human disorders such as chronic infections, inflammatory bowel diseases, obesity, and cancer.

• Bacteria/metabolism
• Bacteriocins/metabolism
• Dysbiosis
• Gastrointestinal Microbiome
• Humans
• Lactobacillales/metabolism
• Probiotics/pharmacology

Streptococcus thermophilus is a Gram-positive bacterium widely used as starter in the dairy industry as well as in many traditional fermented products. In addition to its technological importance, it has also gained interest in recent years as beneficial bacterium due to human health-promoting functionalities. The objective of this study was to inventory the main health-promoting properties of S. thermophilus and to study their intra-species diversity at the genomic and genetic level within a collection of representative strains.

In this study various health-related functions were analyzed at the genome level from 79 genome sequences of strains isolated over a long time period from diverse products and different geographic locations. While some functions are widely conserved among isolates (e.g., degradation of lactose, folate production) suggesting their central physiological and ecological role for the species, others including the tagatose-6-phosphate pathway involved in the catabolism of galactose, and the production of bioactive peptides and gamma-aminobutyric acid are strain-specific. Most of these strain-specific health-promoting properties seems to have been acquired via horizontal gene transfer events. The genetic basis for the phenotypic diversity between strains for some health related traits have also been investigated. For instance, substitutions in the galK promoter region correlate with the ability of some strains to catabolize galactose via the Leloir pathway. Finally, the low occurrence in S. thermophilus genomes of genes coding for biogenic amine production and antibiotic resistance is also a contributing factor to its safety status.

The natural intra-species diversity of S. thermophilus, therefore, represents an interesting source for innovation in the field of fermented products enriched for healthy components that can be exploited to improve human health. A better knowledge of the health-promoting properties and their genomic and genetic diversity within the species may facilitate the selection and application of strains for specific biotechnological and human health-promoting purpose. Moreover, by pointing out that a substantial part of its functional potential still defies us, our work opens the way to uncover additional health-related functions through the intra-species diversity exploration of S. thermophilus by comparative genomics approaches.

The online version contains supplementary material available at 10.1186/s12864-022-08459-y.

• Bacteriocin
• Comparative genomics
• Conjugated linoleic acid
• GABA
• Galactose
• Lactose
• Pangenome
• PrtS
• Vitamin

Background & Aims: Dysbiosis is associated with gastric cancer (GC) development. However, no longitudinal study was carried out to identify key bacteria that could predict for GC progression. Here, we aimed to investigate changes in bacterial metagenome prior to GC and develop a microbiome-based predictive model to accurately classify patients at risk of GC.

Methods: Bacterial 16S rDNA was sequenced from 89 gastric antral biopsies obtained from 43 participants. This study was nested in a prospective, longitudinal study, whereby study participants underwent screening gastroscopy, with further 1-2 yearly surveillance gastroscopies for at least 5 years. Putative bacterial taxonomic and functional features associated with GC carcinogenesis were identified by comparing between controls, patients with gastric intestinal metaplasia (IM) and patients with early gastric neoplasia (EGN).

Results: Patients with EGN had enrichment of Proteobacteria (in particular Proteus genus) and depletion of Bacteroidetes (in particular S24-7 family) in their gastric mucosa. Sequencing identified more patients with Helicobacter pylori compared to histopathological assessment, while H. pylori was also significantly enriched in EGN. Furthermore, a total of 261 functional features, attributing to 97 KEGG pathways were differentially abundant at baseline between patients who subsequent developed EGN (n = 13/39) and those who did not. At the same time, a constellation of six microbial taxonomic features present at baseline, provided the highest classifying power for subsequent EGN (AUC = 0.82).

Conclusion: Our study highlights early microbial changes associated with GC carcinogenesis, suggesting a potential role for prospective microbiome surveillance for GC.

• Helicobacter pylori
• early gastric neoplasia
• gastric cancer
• intestinal metaplasia
• microbiome

• Bacteria
• Carcinogenesis
• Colorectal cancer
• Genotoxicity.
• Gut microbiota
• Inflammation

• CAC
• anti-inflammation
• anti-oxidant
• anti-tumor
• colitis-associated colorectal cancer
• gut microbiota
• polysaccharides
• short-chain fatty acid

• LAB
• fermentation characteristics
• soymilk
• tolerant ability

This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug.

Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (~42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G₂ phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND).

Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0×10¹⁰ – 1.0×10¹¹ CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 10¹¹, 6.75 × 10¹¹, and 13.5×10¹¹ CFU/kg/day; thus the maximum dose was 800–8000-fold higher than the estimated dose for FIH.

In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy.

These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.

• Lactobacillus rhamnosus
• Pediococcus pentosaceus SL4
• biologics
• colorectal cancer
• drug delivery system
• non-clinical trial
• oral administration
• probiotics derived anti-cancer protein P8
• protein secretion system
• therapeutic protein
• toxicology finding