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22 pages, 820 KB  
Review
An Asset for Food Safety: The Knowledge Behind the Physiological Alterations Induced by ETEC Enterotoxins
by Maria Margarida Barros, Ana Maria Campos, Joana Castro, Ricardo Oliveira, Daniela Araújo, Divanildo Outor-Monteiro and Carina Almeida
Foods 2025, 14(21), 3651; https://doi.org/10.3390/foods14213651 - 26 Oct 2025
Viewed by 724
Abstract
Foodborne pathogens represent a significant public health risk in both developed and developing countries. Among these pathogens, enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in humans and one of the leading causes of mortality in newly weaned pigs. The main [...] Read more.
Foodborne pathogens represent a significant public health risk in both developed and developing countries. Among these pathogens, enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in humans and one of the leading causes of mortality in newly weaned pigs. The main sources of ETEC contamination include environments with poor hygiene and contaminated water, meat, cereals, and vegetables. Therefore, this review manuscript focuses on the pathogenesis of ETEC in humans and pigs. The main virulence factors responsible for ETEC-associated infections, such as colonization factors and toxins, will be described for both species, with particular emphasis on the toxins as well as, their classification and structural characterization. More specifically, this study will outline the main physiological alterations and adaptive mechanisms induced by these enterotoxins, namely heat-stable toxin (ST) and heat-labile toxin (LT), in the three most affected systems: the gastrointestinal system, the enteric nervous system (ENS), and the immune system. This set of findings provides a deeper insight into the pathogenesis of this relevant foodborne pathogen, which is crucial for empowering food scientists and stakeholders to more effectively mitigate associated risks. As such, it provides valuable understanding of toxin activity, serving as a means to raise awareness of food safety practices and strengthening risk communication, surveillance and intervention strategies, thereby ensuring consumer protection. Additionally, this knowledge enables the development of preventive strategies to reduce ETEC infections, thereby decreasing the need for clinical management among consumers exposed to this bacterium. Ultimately, it contributes to the preservation of public health, the reduction of antimicrobial use, and the lowering of antimicrobial resistance gene prevalence. Full article
(This article belongs to the Special Issue Feature Reviews on Food Microbiology)
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33 pages, 891 KB  
Review
The Role of Probiotics in Enhancing Animal Health: Mechanisms, Benefits, and Applications in Livestock and Companion Animals
by Sorin Marian Mârza, Camelia Munteanu, Ionel Papuc, Lăcătuş Radu and Robert Cristian Purdoiu
Animals 2025, 15(20), 2986; https://doi.org/10.3390/ani15202986 - 15 Oct 2025
Cited by 6 | Viewed by 5049
Abstract
This review examines the diverse ways in which probiotics, defined as live microorganisms that provide health benefits to the host when administered in adequate amounts, contribute to animal health and welfare across both livestock and companion species. By modulating gut microbiota, enhancing immune [...] Read more.
This review examines the diverse ways in which probiotics, defined as live microorganisms that provide health benefits to the host when administered in adequate amounts, contribute to animal health and welfare across both livestock and companion species. By modulating gut microbiota, enhancing immune responses, and suppressing harmful pathogens, probiotics represent an effective strategy for disease prevention and performance improvement without reliance on antibiotics. In livestock production, these beneficial microbes have been shown to optimize feed utilization, support growth, and reduce methane emissions, thereby contributing to more sustainable farming practices. Their role extends beyond productivity, as probiotics also help mitigate antimicrobial resistance (AMR) by offering natural alternatives to conventional treatments. In aquaculture, they further promote environmental sustainability by improving water quality and reducing pathogen loads. For companion animals such as dogs and cats, probiotics are increasingly recognized for their ability to support gastrointestinal balance, alleviate stress through gut–brain axis interactions, and aid in the management of common conditions including diarrhea, food sensitivities, and allergies. The integration of probiotics into veterinary practice thus reflects a growing emphasis on holistic and preventive approaches to animal health. Despite these advances, several challenges remain, including variability in strain-specific efficacy, regulatory limitations, and cost-effectiveness in large-scale applications. Emerging research into precision probiotics, host–microbiome interactions, and innovative delivery methods offers promising avenues to overcome these barriers. As such, probiotics can be regarded not only as functional supplements but also as transformative tools that intersect animal health, productivity, and sustainability. Full article
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23 pages, 683 KB  
Review
Endometriosis and Nutrition: Therapeutic Perspectives
by Francesco Giuseppe Martire, Eugenia Costantini, Claudia d’Abate, Giovanni Capria, Emilio Piccione and Angela Andreoli
J. Clin. Med. 2025, 14(11), 3987; https://doi.org/10.3390/jcm14113987 - 5 Jun 2025
Cited by 5 | Viewed by 10181
Abstract
Endometriosis is a chronic, hormone-dependent disorder characterized by an inflammatory response. The disease affects approximately 10% of the general female population, with prevalence rates reaching 30–40% in women with dysmenorrhea and 50–60% in those experiencing infertility. In addition to pelvic pain and reproductive [...] Read more.
Endometriosis is a chronic, hormone-dependent disorder characterized by an inflammatory response. The disease affects approximately 10% of the general female population, with prevalence rates reaching 30–40% in women with dysmenorrhea and 50–60% in those experiencing infertility. In addition to pelvic pain and reproductive issues, gastrointestinal symptoms, such as acute abdominal pain, constipation, diarrhea, or alternating bowel habits, are frequently reported and can be highly disabling. Emerging evidence indicates that dietary patterns may modulate the inflammatory environment associated with endometriosis, potentially influencing symptom severity by affecting oxidative stress, estrogen metabolism, and levels of sex hormone-binding globulin (SHBG). Diets rich in antioxidants, polyunsaturated fatty acids (PUFAs), and vitamins D, C, and E—alongside the avoidance of processed foods, red meat, and animal fats—may offer beneficial effects. This narrative review explores the relationship between nutrition and endometriosis, emphasizing the therapeutic potential of dietary interventions as a complementary strategy. Notably, dietary approaches may serve not only to alleviate pain and improve fertility outcomes but also to reduce lesion growth and recurrence, particularly in patients seeking pregnancy or those unable to undergo hormonal therapy due to contraindications. Furthermore, nutritional strategies may enhance postoperative recovery and act as a viable first-line therapy when conventional treatments are not applicable. A total of 250 studies were initially identified through PubMed and Scopus. After removing duplicates and non-relevant articles, 174 were included in this review. Our findings underscore the urgent need for further studies to develop evidence-based, personalized nutritional interventions for managing endometriosis-related symptoms. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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29 pages, 455 KB  
Review
Current Challenges in Yersinia Diagnosis and Treatment
by Bogna Grygiel-Górniak
Microorganisms 2025, 13(5), 1133; https://doi.org/10.3390/microorganisms13051133 - 15 May 2025
Cited by 4 | Viewed by 6723
Abstract
Yersinia bacteria (Yersinia enterocolitica, Yersinia pseudotuberculosis) are commonly found in nature in all climatic zones and are isolated from food (mainly raw pork, unpasteurized milk, or contaminated water), soil, and surface water, rarely from contaminated blood. Yersinia infection occurs through sick or [...] Read more.
Yersinia bacteria (Yersinia enterocolitica, Yersinia pseudotuberculosis) are commonly found in nature in all climatic zones and are isolated from food (mainly raw pork, unpasteurized milk, or contaminated water), soil, and surface water, rarely from contaminated blood. Yersinia infection occurs through sick or asymptomatic carriers and contact with the feces of infected animals. The invasion of specific bacterial serotypes into the host cell is based on the type 3 secretion system (T3SS), which directly introduces many effector proteins (Yersinia outer proteins—Yops) into the host cell. The course of yersiniosis can be acute or chronic, with the predominant symptoms of acute enteritis (rarely pseudo-appendicitis or septicemia develops). Clinical and laboratory diagnosis of yersiniosis is difficult. The infection requires confirmation by isolating Yersinia bacteria from feces or other biological materials, including lymph nodes, synovial fluid, urine, bile, or blood. The detection of antibodies in blood serum or synovial fluid is useful in the diagnostic process. The treatment of yersiniosis is mainly symptomatic. Uncomplicated infections (diarrhea and abdominal pain) usually do not require antibiotic therapy, which is indicated in severe cases. Surgical intervention is undertaken in the situations of intestinal necrosis. Given the diagnostic and therapeutic difficulties, this review discusses the prevalence of Y. enterocolitica and Y. pseudotuberculosis, their mechanisms of disease induction (virulence factors and host response), clinical manifestations, diagnostic and preventive methods, and treatment strategies in the context of current knowledge and available recommendations. Full article
(This article belongs to the Special Issue Advances in Enteric Infections Research)
17 pages, 6227 KB  
Article
A Novel Vaccine for Bovine Diarrhea Complex Utilizing Recombinant Enterotoxigenic Escherichia coli and Salmonella Expressing Surface-Displayed Chimeric Antigens from Enterohemorrhagic Escherichia coli O157:H7
by Hernán Ramírez, Daniel A. Vilte, Daniela Hozbor, Eugenia Zurita, Daniela Bottero, María C. Casabonne, Ángel A. Cataldi, Andrés Wigdorovitz and Mariano Larzábal
Vaccines 2025, 13(2), 124; https://doi.org/10.3390/vaccines13020124 - 25 Jan 2025
Viewed by 2153
Abstract
Background/Objectives: Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a zoonotic pathogen primarily found in cattle, causes Hemolytic Uremic Syndrome (HUS) in humans, often through contaminated food. Its Type Three Secretion System (T3SS) facilitates gut colonization. In contrast, neonatal calf diarrhea (NCD) is mainly caused by [...] Read more.
Background/Objectives: Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a zoonotic pathogen primarily found in cattle, causes Hemolytic Uremic Syndrome (HUS) in humans, often through contaminated food. Its Type Three Secretion System (T3SS) facilitates gut colonization. In contrast, neonatal calf diarrhea (NCD) is mainly caused by pathogens like enterotoxigenic Escherichia coli (ETEC), Salmonella spp., Bovine Coronavirus (BCoV), and Bovine Rotavirus type A (BRoVA). This study engineered a chimeric protein combining EspB and Int280γ, two T3SS components, expressed in the membranes of Salmonella Dublin and ETEC. Methods: Immune responses in vaccinated mice and guinea pigs were assessed through ELISA assays. Results: Successful membrane anchorage and stability of the chimera were confirmed. Immune evaluations showed no enhancement from combining recombinant bacteria, indicating either bacterium suffices in a single formulation. Chimeric expression yielded immunogenicity equivalent to 10 µg of recombinant protein, with similar antibody titers. IgG1/IgG2a levels and Th1, Th2, and Th17 markers indicated a mixed immune response, providing broad humoral and cellular protection. Responses to BCoV, BRoVA, ETEC, and Salmonella antigens remained strong and did not interfere with chimera-specific responses, potentially boosting NCD vaccine efficacy. Conclusions: The chimera demonstrated robust immunogenicity, supporting its potential as a viable vaccine candidate against EHEC O157:H7. This approach could enhance NCD vaccine valency by offering broader protection against calf diarrhea while reducing HUS transmission risks to humans. Full article
(This article belongs to the Special Issue Vaccines and Passive Immune Strategies in Veterinary Medicine)
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21 pages, 1301 KB  
Review
Medicinal Cannabis and the Intestinal Microbiome
by Luis Vitetta, Tamara Nation, Debbie Oldfield and Michael Thomsen
Pharmaceuticals 2024, 17(12), 1702; https://doi.org/10.3390/ph17121702 - 17 Dec 2024
Cited by 5 | Viewed by 8360
Abstract
Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries. The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain [...] Read more.
Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries. The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea. It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut–microbiota–brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems. An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity. This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota. We advance an exogenous cannabinoid–intestinal microbiota–endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis. Full article
(This article belongs to the Special Issue Therapeutic Potential for Cannabinoid and Its Receptor)
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16 pages, 2272 KB  
Article
Alterations in the Microbiomes and Metabolic Profiles of the Ileal Between the Hu Sheep and East Friesian Sheep
by Wenna Yao, Yue Zhao, Shuo Yan, Huimin Zhang, Teligun Bao, Siqin Bao, Xihe Li and Yongli Song
Int. J. Mol. Sci. 2024, 25(24), 13267; https://doi.org/10.3390/ijms252413267 - 10 Dec 2024
Cited by 2 | Viewed by 1717
Abstract
The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu [...] Read more.
The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu sheep. Gut microbiota and metabolites play a role in host disease resistance. The intestinal bacterial microbiota is essential for maintaining the health of sheep and ensuring their productive potential, and it may also help explain disease-resistant phenotypic differences related to breeds. However, the ileum microbiota and metabolite profiles of Hu sheep and East Friesian sheep have remained poorly characterized. The ileal is a significant organ in the intestinal tract, and most nutrients and minerals in food are absorbed through the small intestine. It is necessary to understand the composition of both species’ ileal microbiota and metabolites using the same feeding conditions. Therefore, studying the differences in the ileal microorganisms between breeds is essential to decipher the mechanisms behind these differences and identify microorganisms that influence the disease-resistant phenotype drive of ruminants. Due to the poor disease-resistant phenotype in sheep during the weaning period, with diarrhea and other diseases most likely to occur, we selected dairy sheep that were just two months old and had recently been weaned. This study comprehensively examined differences between the ileal microbiota in a large cohort of two breeds of sheep, including six Hu sheep and six East Friesian sheep. Using 16S rRNA and non-targeted metabolomics analysis, we determined that the Hu sheep had more microorganisms, including Lactobacillus, Bifidobacterium, Streptococcus, and Limmosilactobacillus, and more metabolites, including 2,7-Dihydroxy-5-methyl-1-naphthoic acid, Leu-Pro-Glu-Phe-Tyr, dodecanoic acid, Ala-Gln-Phe-Ile-Met, and Ala-Gln-Glu-Val-His, compared to the EF sheep group. Moreover, the Hu sheep were significantly enriched in amino acid biosynthesis, fatty acid metabolites, and bile secretion compared to the EF sheep groups, which may have been the main driver of the observed differences in disease-resistant phenotypes between the Hu sheep and East Friesian sheep. In addition, we hypothesized that there may be multiple beneficial microbes and metabolites that modulate the immune response and ultimately affect disease resistance. Therefore, these findings provide insights into the mechanisms underlying disease-resistant phenotype in sheep and may provide useful information for optimizing the composition of the ileal bacterial microbiota in sheep. Full article
(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)
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11 pages, 251 KB  
Article
Retrospective Study of 222 Dogs Suffering from Food-Responsive Enteropathy—Correlation with Clinical Variables, Diet and Breed
by Alessia Candellone, Gaia Raviri, Vittorio Saettone, Martine Didier, Giacomo Rossi, Andrea Marchegiani, Alessandra Gavazza, Alessandro Di Cerbo and Matteo Cerquetella
Vet. Sci. 2024, 11(7), 294; https://doi.org/10.3390/vetsci11070294 - 1 Jul 2024
Cited by 1 | Viewed by 7001
Abstract
Food-responsive enteropathy (FRE) is the most frequent form of canine chronic inflammatory enteropathy (CIE). It can be diagnosed if, after excluding known causes of diarrhea, clinical signs resolve or significantly improve after an appropriate dietary trial. No universal diet can resolve the clinical [...] Read more.
Food-responsive enteropathy (FRE) is the most frequent form of canine chronic inflammatory enteropathy (CIE). It can be diagnosed if, after excluding known causes of diarrhea, clinical signs resolve or significantly improve after an appropriate dietary trial. No universal diet can resolve the clinical signs in every case of FRE, as genetic predisposition and environment (e.g., the possible role of the diet feed before the disease onset) are suggested as possible players. The study aimed to retrospectively evaluate the possible correlations between disease, diet, and breed in a large cohort of dogs (n = 222) suffering from FRE. Throughout the study, dogs differed based on dietary options: commercial diet group, homemade diet group, and mixed diet group. Diet, breed, age, body weight, body condition score (BCS), fecal score (FS), canine chronic enteropathy activity index (CCECAI), and selected clinical signs were variably evaluated at T0 and at final time (FT—based on response to the diet[s], but between 30 and 60 days). Significant differences between T0 and FT were found regarding FS, BCS, and CCECAI, as well as between age, BCS, and CCECAI at FT with the FS at FT. The CCECAI at FT was significantly directly correlated only with the shift from a mixed to a homemade diet. Finally, the multiple linear regression analysis between the covariables of different breeds versus clinical response to the dietary trials did not highlight any difference except for the passage from commercial to mixed diet in a specific subgroup of breeds. The present study reports the clinical progression in 222 dogs suffering from FRE, and it could represent a reference for the variables investigated, considering the large number of patients included. Full article
(This article belongs to the Special Issue Small Animal Gastrointestinal Diseases: Challenges and Advances)
16 pages, 1492 KB  
Article
Supplementation of Foals with a Saccharomyces cerevisiae Fermentation Product Alters the Early Response to Vaccination
by Eva Ronja Terpeluk, Jana Schäfer, Christa Finkler-Schade and Hans-Joachim Schuberth
Animals 2024, 14(6), 960; https://doi.org/10.3390/ani14060960 - 20 Mar 2024
Cited by 2 | Viewed by 2636
Abstract
Feed supplements supporting animal welfare and performance are becoming increasingly important. Immunomodulatory effects of such products have been observed in many species. The aim of this study was to analyze whether food supplementation with a Saccharomyces cerevisiae fermentation product (SCFP) affects the occurrence [...] Read more.
Feed supplements supporting animal welfare and performance are becoming increasingly important. Immunomodulatory effects of such products have been observed in many species. The aim of this study was to analyze whether food supplementation with a Saccharomyces cerevisiae fermentation product (SCFP) affects the occurrence of foal diarrhea in early life, and whether the SCFP feeding has an impact on the immediate response to a parenteral vaccination at the age of 6–9 months. Eleven foals received the SCFP (OLI) and eleven foals were fed a placebo (PLA) for 29 days. Growth, diarrhea, and diarrhea severity were observed until day 30. After weaning, at the age of 6–9 months, foals were vaccinated parenterally against influenza and tetanus. The supplementation had no statistically significant effect on diarrhea duration and severity. On the day of vaccination, PLA and OLI foals did not differ significantly regarding numbers of circulating blood leukocyte subsets. However, the response to vaccination differed significantly between OLI and PLA foals. In OLI foals, the numbers of the major leukocyte fractions (granulocytes, lymphocytes, monocytes, CD4+ T cells, CD8+ T cells, CD21+ B cells, and MHC-II+/CD21− cells) increased significantly 24 h after vaccination but remained unchanged in PLA foals. The observed results suggest that early life supplementation with an SCFP may affect the early immune response to an initial vaccination. Full article
(This article belongs to the Special Issue Focus on Gut Health in Horses: Current Research and Approaches)
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56 pages, 4576 KB  
Review
The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs
by Muhammad Safiullah Virk, Muhammad Abdulrehman Virk, Yufeng He, Tabussam Tufail, Mehak Gul, Abdul Qayum, Abdur Rehman, Arif Rashid, John-Nelson Ekumah, Xu Han, Junxia Wang and Xiaofeng Ren
Nutrients 2024, 16(4), 546; https://doi.org/10.3390/nu16040546 - 16 Feb 2024
Cited by 90 | Viewed by 31648
Abstract
Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is [...] Read more.
Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors. Full article
(This article belongs to the Special Issue Effects of Probiotics on Inflammation and Health Outcomes)
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16 pages, 3364 KB  
Article
Comparative Transcriptome Analysis of Shiga Toxin-Producing Escherichia coli O157:H7 on Bovine Rectoanal Junction Cells and Human Colonic Epithelial Cells during Initial Adherence
by Lekshmi K. Edison, Indira T. Kudva and Subhashinie Kariyawasam
Microorganisms 2023, 11(10), 2562; https://doi.org/10.3390/microorganisms11102562 - 15 Oct 2023
Cited by 7 | Viewed by 2662
Abstract
Shiga toxin-producing Escherichia coli (STEC) are notorious foodborne pathogens, capable of causing severe diarrhea and life-threatening complications in humans. Cattle, acting as both primary reservoirs and asymptomatic carriers of STEC, predominantly harbor the pathogen in their rectoanal junction (RAJ), facilitating its transmission to [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) are notorious foodborne pathogens, capable of causing severe diarrhea and life-threatening complications in humans. Cattle, acting as both primary reservoirs and asymptomatic carriers of STEC, predominantly harbor the pathogen in their rectoanal junction (RAJ), facilitating its transmission to humans through contaminated food sources. Despite the central role of cattle in STEC transmission, the molecular mechanisms governing STEC’s adaptation in the RAJ of the asymptomatic reservoir host and its subsequent infection of human colonic epithelial cells, resulting in diarrhea, remain largely unexplored. This study aims to uncover these complicated dynamics by focusing on the STEC O157:H7 serotype within two distinct host environments, bovine RAJ cells and human colonic epithelial cells, during initial colonization. We employed comparative transcriptomics analysis to investigate differential gene expression profiles of STEC O157:H7 during interactions with these cell types. STEC O157:H7 was cultured either with bovine RAJ cells or the human colonic epithelial cell line CCD CoN 841 to simulate STEC-epithelial cell interactions within these two host species. High-throughput RNA sequencing revealed 829 and 1939 bacterial genes expressed in RAJ and CCD CoN 841, respectively. After gene filtering, 221 E. coli O157:H7 genes were upregulated during initial adherence to CCD CoN cells and 436 with RAJ cells. Furthermore, 22 genes were uniquely expressed with human cells and 155 genes with bovine cells. Our findings revealed distinct expression patterns of STEC O157:H7 genes involved in virulence, including adherence, metal iron homeostasis, and stress response during its initial adherence (i.e., six hours post-infection) to bovine RAJ cells, as opposed to human colonic epithelial cells. Additionally, the comparative analysis highlighted the potential role of some genes in host adaptation and tissue-specific pathogenicity. These findings shed new light on the potential mechanisms of STEC O157:H7 contributing to colonize the intestinal epithelium during the first six hours of infection, leading to survival and persistence in the bovine reservoir and causing disease in humans. Full article
(This article belongs to the Special Issue Shiga-Toxin Producing Escherichia coli and the Animal Host)
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18 pages, 1777 KB  
Article
Shiga-Toxin-Producing Strains of Escherichia coli O104:H4 and a Strain of O157:H7, Which Can Cause Human Hemolytic Uremic Syndrome, Differ in Biofilm Formation in the Presence of CO2 and in Their Ability to Grow in a Novel Cell Culture Medium
by Kei Amemiya, David A. Rozak, Jennifer L. Dankmeyer, William R. Dorman, Charles Marchand, David P. Fetterer, Patricia L. Worsham and Brett K. Purcell
Microorganisms 2023, 11(7), 1744; https://doi.org/10.3390/microorganisms11071744 - 3 Jul 2023
Cited by 7 | Viewed by 3198
Abstract
One pathogen that commonly causes gastrointestinal illnesses from the consumption of contaminated food is Escherichia coli O157:H7. In 2011 in Germany, however, there was a prominent outbreak of bloody diarrhea with a high incidence of hemolytic uremic syndrome (HUS) caused by an atypical, [...] Read more.
One pathogen that commonly causes gastrointestinal illnesses from the consumption of contaminated food is Escherichia coli O157:H7. In 2011 in Germany, however, there was a prominent outbreak of bloody diarrhea with a high incidence of hemolytic uremic syndrome (HUS) caused by an atypical, more virulent E. coli O104:H4 strain. To facilitate the identification of this lesser-known, atypical E. coli O104:H4 strain, we wanted to identify phenotypic differences between it and a strain of O157:H7 in different media and culture conditions. We found that E. coli O104:H4 strains produced considerably more biofilm than the strain of O157:H7 at 37 °C (p = 0.0470–0.0182) Biofilm production was significantly enhanced by the presence of 5% CO2 (p = 0.0348–0.0320). In our study on the innate immune response to the E. coli strains, we used HEK293 cells that express Toll-like receptors (TLRs) 2 or 4. We found that E. coli O104:H4 strains had the ability to grow in a novel HEK293 cell culture medium, while the E. coli O157:H7 strain could not. Thus, we uncovered previously unknown phenotypic properties of E. coli O104:H4 to further differentiate this pathogen from E. coli O157:H7. Full article
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16 pages, 3464 KB  
Article
Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol
by Daniela Eliza Marin and Ionelia Taranu
Toxins 2023, 15(7), 421; https://doi.org/10.3390/toxins15070421 - 28 Jun 2023
Cited by 8 | Viewed by 3942
Abstract
Alternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for [...] Read more.
Alternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for alternariol and its metabolites using an in silico working model based on the MetaTox, SwissADME, pKCMS, and PASS online computational programs. A number of 12 metabolites were identified as corresponding to the metabolomic profile of alternariol. ADME profile for AOH and predicted metabolites indicated a moderate or high intestinal absorption probability but a low probability to penetrate the blood–brain barrier. In addition to cytotoxic, mutagenic, carcinogenic, and endocrine disruptor effects, the computational model has predicted other toxicological endpoints for the analyzed compounds, such as vascular toxicity, haemato-toxicity, diarrhea, and nephrotoxicity. AOH and its metabolites have been predicted to act as a substrate for different isoforms of phase I and II drug-metabolizing enzymes and to interact with the response to oxidative stress. In conclusion, in silico methods can represent a viable alternative to in vitro and in vivo tests for the prediction of mycotoxins metabolism and toxicity. Full article
(This article belongs to the Section Mycotoxins)
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20 pages, 714 KB  
Review
Gilteritinib: The Story of a Proceeding Success into Hard-to-Treat FLT3-Mutated AML Patients
by Matteo Molica, Salvatore Perrone and Marco Rossi
J. Clin. Med. 2023, 12(11), 3647; https://doi.org/10.3390/jcm12113647 - 24 May 2023
Cited by 25 | Viewed by 7579
Abstract
The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction of tyrosine kinase inhibitors (TKI) into clinics, such as midostaurin and gilteritinib. The present work summarizes [...] Read more.
The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction of tyrosine kinase inhibitors (TKI) into clinics, such as midostaurin and gilteritinib. The present work summarizes the clinical data that led to the use of gilteritinib in clinical practice. Gilteritinib is a second-generation TKI with deeper single-agent activity than first-generation drugs against both FLT3–ITD and TKD mutations in human studies. Moreover, the phase I/II dose-escalation, dose-expansion Chrysalis trial showed an acceptable safety profile of gilteritinib (diarrhea, elevated aspartate aminotransferase, febrile neutropenia, anemia, thrombocytopenia, sepsis, and pneumonia) and a 49% overall response rate (ORR) in 191 FLT3-mutated relapsed/refractory (R/R) AML patients. In 2019, the pivotal ADMIRAL trial showed that the median overall survival was significantly longer in patients treated with gilteritinib than among those receiving chemotherapy (9.3 vs. 5.6 months, respectively) and the ORR to gilteritinib was 67.6%, outperforming the 25.8% for chemotherapy arm and leading to the license for its clinical use by the US Food and Drug Administration. Since then, several real-world experiences have confirmed the positive results in the R/R AML setting. Finally, gilteritinib-based combinations currently under investigation, with several compounds (venetoclax, azacitidine, conventional chemotherapy, etc.) and some practical tips (maintenance after allogeneic transplantation, interaction with antifungal drugs, extramedullary disease, and onset of resistance), will be analyzed in detail in this review. Full article
(This article belongs to the Special Issue Recent Progress in Leukemia: Where Do We Stand?)
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17 pages, 745 KB  
Review
Molecular Targets in Campylobacter Infections
by Markus M. Heimesaat, Steffen Backert, Thomas Alter and Stefan Bereswill
Biomolecules 2023, 13(3), 409; https://doi.org/10.3390/biom13030409 - 22 Feb 2023
Cited by 21 | Viewed by 6236
Abstract
Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients [...] Read more.
Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients develop abdominal pain and diarrhea. Post-infectious disorders following acute enteritis may occur and affect the nervous system, the joints or the intestines. Immunocompromising comorbidities in infected patients favor bacteremia, leading to vascular inflammation and septicemia. Prevention of human infection is achieved by hygiene measures focusing on the reduction of pathogenic food contamination. Molecular targets for the treatment and prevention of campylobacteriosis include bacterial pathogenicity and virulence factors involved in motility, adhesion, invasion, oxygen detoxification, acid resistance and biofilm formation. This repertoire of intervention measures has recently been completed by drugs dampening the pro-inflammatory immune responses induced by the Campylobacter endotoxin lipo-oligosaccharide. Novel pharmaceutical strategies will combine anti-pathogenic and anti-inflammatory effects to reduce the risk of both anti-microbial resistance and post-infectious sequelae of acute enteritis. Novel strategies and actual trends in the combat of Campylobacter infections are presented in this review, alongside molecular targets applied for prevention and treatment strategies. Full article
(This article belongs to the Special Issue Molecular Targets in Campylobacter Infections)
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