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Keywords = antimicrobial-associated diarrhea

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36 pages, 539 KiB  
Review
Genomic Adaptation, Environmental Challenges, and Sustainable Yak Husbandry in High-Altitude Pastoral Systems
by Saima Naz, Ahmad Manan Mustafa Chatha, Qudrat Ullah, Muhammad Farooq, Tariq Jamil, Raja Danish Muner and Azka Kiran
Vet. Sci. 2025, 12(8), 714; https://doi.org/10.3390/vetsci12080714 - 29 Jul 2025
Viewed by 204
Abstract
The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. [...] Read more.
The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. This review presents the genomic, physiological, and environmental dimensions of yak biology and husbandry. Genes such as EPAS1, which encodes hypoxia-inducible transcription factors, underpin physiological adaptations, including enlarged cardiopulmonary structures, elevated erythrocyte concentrations, and specialized thermoregulatory mechanisms that enable their survival at elevations of 3000 m and above. Copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) present promising markers for improving milk and meat production, disease resistance, and metabolic efficiency. F1 and F2 generations of yak–cattle hybrids show superior growth and milk yields, but reproductive barriers, such as natural mating or artificial insemination, and environmental factors limit the success of these hybrids beyond second generation. Infectious diseases, such as bovine viral diarrhea and antimicrobial-resistant and biofilm-forming Enterococcus and E. coli, pose risks to herd health and food safety. Rising ambient temperatures, declining forage biomass, and increased disease prevalence due to climate changes risk yak economic performance and welfare. Addressing these challenges by nutritional, environmental, and genetic interventions will safeguard yak pastoralism. This review describes the genes associated with different yak traits and provides an overview of the genetic adaptations of yaks (Bos grunniens) to environmental stresses at high altitudes and emphasizes the need for conservation and improvement strategies for sustainable husbandry of these yaks. Full article
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19 pages, 6650 KiB  
Article
Multi-Strain Probiotic Regulates the Intestinal Mucosal Immunity and Enhances the Protection of Piglets Against Porcine Epidemic Diarrhea Virus Challenge
by Xueying Wang, Qi Zhang, Weijian Wang, Xiaona Wang, Baifen Song, Jiaxuan Li, Wen Cui, Yanping Jiang, Weichun Xie and Lijie Tang
Microorganisms 2025, 13(8), 1738; https://doi.org/10.3390/microorganisms13081738 - 25 Jul 2025
Viewed by 366
Abstract
Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, [...] Read more.
Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article
(This article belongs to the Special Issue Viral Infection on Swine: Pathogenesis, Diagnosis and Control)
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18 pages, 3219 KiB  
Article
Mobilome of Environmental Isolates of Clostridioides difficile
by Khald Blau and Claudia Gallert
Antibiotics 2025, 14(7), 678; https://doi.org/10.3390/antibiotics14070678 - 4 Jul 2025
Viewed by 432
Abstract
Background/Objectives: Clostridioides difficile is a “One Health” pathogen and a cause of antibiotics-associated diarrhea and pseudomembranous colitis. Mobile genetic elements (MGEs) have been documented in the genomes of clinical C. difficile strains; however, the presence of MGEs in environmental strains remains poorly characterized. [...] Read more.
Background/Objectives: Clostridioides difficile is a “One Health” pathogen and a cause of antibiotics-associated diarrhea and pseudomembranous colitis. Mobile genetic elements (MGEs) have been documented in the genomes of clinical C. difficile strains; however, the presence of MGEs in environmental strains remains poorly characterized. Thus, the present study was conducted with the objective of identifying the prevalence of MGEs, including mobilizable transposons (MTns), conjugative transposons (CTns), plasmids, and insertion sequences, in whole genome sequences (WGSs) of environmental C. difficile isolates. Methods: The analysis of MGEs was conducted using 166 WGSs obtained from C. difficile strains isolated from various environmental sources contaminated with feces. The MGEs were identified using bioinformatic tools. Results: A total of 48.2% (80/166) of the studied genomes were identified to harbor nine transposons, including Tn916, Tn6194-like, Tn5397, Tn6215, Tn4001, Tn6073, Tn6110, Tn6107, or Tn5801-like. The majority of MTns and CTns could be found within C. difficile sequence types ST11, ST3, and ST35. The results demonstrated close genetic relatedness among the studied genomes, the array of antimicrobial resistance (AMR) genes, such as tetM, ermB, and aac(6′)-aph(2″), and the presence of CTns. Furthermore, the analysis revealed that 24.7% (41/166) of the genome sequences of isolates were associated with various predominant plasmid groups, including pCD6, pCD-ECE4-6, pCD-WTSI1-4, pCDBI1, and pCd1_3, which belonged to 16 different sequence types. Furthermore, several plasmids were identified as harboring the prophage phiCDHM19. Conclusions: The results of the current study suggest that the identified plasmids are abundant and may encode functions that are relevant to C. difficile physiology. The genomes of C. difficile strains examined contain closely related CTns, suggesting that horizontal transfer of AMR is important in this species or other bacterial species. Further research is required to ascertain the effect of these genetic elements and their transferability on the biology of C. difficile. Full article
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19 pages, 2535 KiB  
Article
The Effects of Recombinant pBD2 on the Growth Performance, Antioxidant Capacity, Immune Function, Intestinal Barrier, and Microbiota of Weaned Piglets
by Zhanwei Teng, Qing Meng, Mengting Ren, Bingke Lv, Liping Yuan, Ningning Zhang, Qinghua Wang, Kun Zhang and Chunli Li
Microorganisms 2025, 13(7), 1443; https://doi.org/10.3390/microorganisms13071443 - 20 Jun 2025
Viewed by 577
Abstract
Defensins, one of the members of the antimicrobial peptide family, play a vital role in resisting microbial invasion and immune regulation. Porcine β-defensin 2 possesses excellent stability, making it an ideal antibiotic alternative for feed additives. In this study, a total of 15 [...] Read more.
Defensins, one of the members of the antimicrobial peptide family, play a vital role in resisting microbial invasion and immune regulation. Porcine β-defensin 2 possesses excellent stability, making it an ideal antibiotic alternative for feed additives. In this study, a total of 15 piglets were used to investigate the effects of supplementing diets with 2.5 mg/kg (LP group) and 5 mg/kg (HP group) of pBD2 to weaned piglets. The results revealed that pBD2 significantly increased the total weight gain and average daily weight gain (p < 0.05), the contents of T-AOC, SOD, IgM, and IL-10 in serum (p < 0.05), the villus-to-crypt ratios, and the expression of tight-junction proteins ZO-1 and claudin-1 (p < 0.05) in the small intestine. Furthermore, pBD2 increased the abundance of beneficial bacteria related to nutrient and energy metabolism while decreasing the abundance of harmful bacteria associated with intestinal inflammation and diarrhea. Alterations in the gut microbiota were closely associated with the levels of T-AOC, SOD, IgM, and IL-10 in serum. pBD2 primarily enhanced the health of weaned piglets by influencing antioxidant capacity, intestinal barrier function, and the intestinal microbiota. Our research provides a novel perspective for addressing the issue of antibiotic residues in feed. Full article
(This article belongs to the Section Gut Microbiota)
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13 pages, 488 KiB  
Article
Use of Probiotics During Antibiotic Therapy in Pediatrics: A Cross-Sectional Survey of Italian Primary Care Pediatricians
by Giacomo Biasucci, Maria Elena Capra, Antonella Giudice, Delia Monopoli, Brigida Stanyevic, Roberta Rotondo, Alessandro Mucci, Cosimo Neglia, Beatrice Campana and Susanna Esposito
Antibiotics 2025, 14(6), 577; https://doi.org/10.3390/antibiotics14060577 - 4 Jun 2025
Viewed by 779
Abstract
Background: Antibiotic-associated diarrhea (AAD) is a common adverse effect of pediatric antibiotic therapy, often linked to gut microbiota disruption. Probiotics may help prevent AAD when appropriately selected and dosed. Methods: We conducted a cross-sectional survey to assess the attitudes and prescribing habits [...] Read more.
Background: Antibiotic-associated diarrhea (AAD) is a common adverse effect of pediatric antibiotic therapy, often linked to gut microbiota disruption. Probiotics may help prevent AAD when appropriately selected and dosed. Methods: We conducted a cross-sectional survey to assess the attitudes and prescribing habits of Italian Primary Care Pediatricians (PCPs) regarding the use of probiotics during antibiotic treatment. A digital questionnaire comprising 23 mandatory multiple-choice items was distributed to 980 PCPs across Italy between July and October 2024. The survey explored probiotic prescribing frequency, indications, strains used, dosage, duration, and sources of information. Descriptive statistics and subgroup analyses by years of clinical experience were performed. Results: A total of 279 PCPs (response rate: 28%) completed the survey; 66.7% were female, and 77.1% had over 20 years of clinical experience. Probiotics were prescribed primarily to restore microbiota balance (81.1%) and prevent AAD (47.3%). The most common barriers included additional cost (35.1%) and perceived lack of evidence (26.5%). Lactobacillus rhamnosus GG (91.8%) and Saccharomyces boulardii (41.9%) were the most frequently recommended strains. Daily doses of 5–10 billion CFU were preferred by 44.4% of respondents, with typical durations of 1–2 weeks (40.1%) or one week (31.2%). Conclusions: Probiotics are widely used by Italian PCPs during antibiotic therapy, especially for microbiota support and AAD prevention. However, variability in practice underscores the need for clearer, evidence-based guidelines regarding probiotic strain selection, dosing, and treatment duration. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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15 pages, 755 KiB  
Article
Vaccination with a Live Avirulent E. coli Vaccine Resulted in Improved Production Performance Combined with a Significant Reduction in Antimicrobial Use
by Frédéric Vangroenweghe, Thomas Matthijs and Marnix Sinnaeve
Antibiotics 2025, 14(6), 547; https://doi.org/10.3390/antibiotics14060547 - 27 May 2025
Viewed by 469
Abstract
Background/Objectives: In swine production, the post-weaning period has been identified as one of the most challenging and stressful periods in the life of a piglet due to changes in its environment and feeding regimen. During this period, piglets might undergo infectious challenges with [...] Read more.
Background/Objectives: In swine production, the post-weaning period has been identified as one of the most challenging and stressful periods in the life of a piglet due to changes in its environment and feeding regimen. During this period, piglets might undergo infectious challenges with enterotoxigenic Escherichia coli (ETEC) resulting in post-weaning diarrhea (PWD), and meningitis due to Streptococcus suis. Therefore, metaphylactic and curative antimicrobial therapy is frequently applied, which leads to an increased treatment incidence per 100 days at risk (TI100). Methods: Here, we report the results of an antimicrobial coaching trajectory in a 1000-sow farm with high antimicrobial use during the post-weaning period. For a period of 21 weeks, we evaluated the effect of an oral live avirulent E. coli F4F18 vaccine (Coliprotec® F4F18; Elanco AH) for the active immunization of piglets against PWD caused by F4- and F18-ETEC on the reduction in antimicrobial use during the post-weaning period. A 1000-sow farm with PIC sows operating in a 1-week BMS was rated as an ‘attention farm’ at the level of the post-weaning period according to the Antimicrobial Consumption and Resistance in Animals (AMCRA) benchmark reporting tool. To analyze the specific approach towards antimicrobial use and the related post-weaning pathology, a farm visit including a biosecurity check was carried out together with all associated stakeholders. Subsequently, an antimicrobial coaching trajectory was utilized to follow-up on the improvement of the reduction in antimicrobial use after implementation of the various pieces of advice. Results: For analytical purposes, we compared the results obtained in period 1 (P1; vaccination week 1–6) to period 2 (P2; vaccination week 7–21), since practical field experience has demonstrated that a ‘stabilization period’ of about 6 weeks is necessary to obtain the maximal effect of vaccination. There was a significant reduction in mortality (5.7% to 2.0%) and improvement in the average daily weight gain (366 g/d to 392 g/d) following vaccination, with a simultaneous reduction in the number of days in nursery (45 days to 38 days). Meanwhile, the weight at the end of nursery remained at a similar level. There was a clinically relevant though non-significant decrease in the TI100 (32.8 days to 20.6 days). Overall, the implementation of all measures resulted in a positive ROI of 2.72 per piglet. Conclusions: The implementation of several biosecurity measures in combination with the use of an oral live avirulent E. coli F4F18 vaccine (Coliprotec F4F18) could improve performance parameters and reduce mortality, while reducing the number of days in nursery and the TI100. Overall, a positive return on investment of 2.72 could be obtained per piglet produced under these improved conditions. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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15 pages, 1501 KiB  
Article
Curcumin Reverses Antibiotic Resistance and Downregulates Shiga Toxin Expression in Enterohemorrhagic E. coli
by Martin Zermeño-Ruiz, Mirian Cobos-Vargas, Mauro Donaldo Saucedo-Plascencia, Rafael Cortés-Zárate, Leonardo Hernandez-Hernandez, Teresa Arcelia Garcia-Cobian, Teresa Estrada-Garcia and Araceli Castillo-Romero
Diseases 2025, 13(5), 154; https://doi.org/10.3390/diseases13050154 - 17 May 2025
Viewed by 569
Abstract
Background: Enterohemorrhagic Escherichia coli (EHEC) is a considerable public health concern associated with several foodborne outbreaks of bloody diarrhea (BD) and the potentially lethal hemolytic uremic syndrome (HUS), the pathophysiology of which is attributable to the Shiga toxin (Stx) produced by this bacterium. [...] Read more.
Background: Enterohemorrhagic Escherichia coli (EHEC) is a considerable public health concern associated with several foodborne outbreaks of bloody diarrhea (BD) and the potentially lethal hemolytic uremic syndrome (HUS), the pathophysiology of which is attributable to the Shiga toxin (Stx) produced by this bacterium. In most patients, supportive treatment will be sufficient; however, in some cases, antibiotic treatment may be necessary. Most antibiotics are not recommended for EHEC infection treatment, particularly those that kill the bacteria, since this triggers the release of Stx in the body, inducing or worsening HUS. Azithromycin, which prevents the release of Stx and is a weaker inducer of the SOS system, has been successfully used to reduce EHEC shedding. It is necessary to identify compounds that eliminate EHEC without inducing Stx release. The use of natural compounds such as curcumin (CUR), a polyphenol derived from turmeric, has been highlighted as an alternative bactericidal treatment approach. Objective: The objective of this study was to establish the effect of CUR and its interactions with selected antibiotics on resistant EHEC O157/H7/EDL933. Methods: Bacterial cultures were exposed to CUR at three different concentrations (110, 220, and 330 µg/mL) and 1.2% DMSO, and the antimicrobial activity of CUR was assessed by measuring the optical density at 600 nm (OD600). The synergy of CUR and the antibiotics was determined with the FIC method. RT-PCR was performed to determine the expression levels of the blaCTX-M-15, catA1, acrAB-tolC stx2A, and stx2B genes. Results: Our data indicate that CUR did not affect the growth of EHEC, but when combined with the antibiotics, it acted as a bacterial resistance breaker. Synergistic combinations of CUR and cefotaxime or chloramphenicol significantly reduced colony counts. Conclusions: Our findings support the potential of CUR as a sensitizer or in combination therapy against EHEC. Full article
(This article belongs to the Section Infectious Disease)
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18 pages, 2023 KiB  
Article
Antimicrobial Activity of a Synthetic Brevibacillin Analog Against Multidrug-Resistant Campylobacter spp.
by Khaled Abdallah, Omar Fliss, Nguyen Phuong Pham, Louis David Guay, Hélène Gingras, Chantal Godin, Philippe Leprohon, Eric Biron, Ismail Fliss and Marc Ouellette
Int. J. Mol. Sci. 2025, 26(10), 4657; https://doi.org/10.3390/ijms26104657 - 13 May 2025
Viewed by 705
Abstract
Campylobacter spp. is one of the most prevalent causes of zoonotic foodborne infections associated with diarrhea in humans. The growing threat of antibiotic resistance calls for innovative approaches. The antimicrobial lipopeptide brevibacillin produced by Brevibacillus laterosporus and its synthetic analog brevibacillin Thr1 showed [...] Read more.
Campylobacter spp. is one of the most prevalent causes of zoonotic foodborne infections associated with diarrhea in humans. The growing threat of antibiotic resistance calls for innovative approaches. The antimicrobial lipopeptide brevibacillin produced by Brevibacillus laterosporus and its synthetic analog brevibacillin Thr1 showed promising activity against Salmonella and E. coli. The latter is a 1602.13 Da positively charged (+3) synthetic peptide of 13 residues that showed reduced cytotoxicity (IC50 of 32.2 µg/mL against Caco-2 cells) and hemolytic activity (1.2% hemolysis at 128 µg/mL) compared to the native peptide. It contains an N-terminal L-isoleucic fatty acid chain and four non-proteinogenic amino acids and ends with valinol at its C-terminus. One key structural modification is the substitution of α,β-dehydrobutyric acid with threonine. We investigated the antimicrobial potential of the synthetic brevibacillin Thr1 analog against a collection of 44 clinical Campylobacter spp. that were obtained from two reference laboratories. Susceptibility testing revealed marked resistance to ciprofloxacin, tetracycline, and ampicillin among the strains, with more than half expressing a multidrug-resistant phenotype. The genomes of the 44 strains were sequenced to study the genes responsible for their antimicrobial resistance. Tetracycline resistance was associated with tet(O), ciprofloxacin resistance with mutations in gyrA and regulatory sequences modulating the expression of an efflux system, and aminoglycoside resistance with genes of the aph family. The brevibacillin Thr1 analog was produced by chemical synthesis, and evaluation of its activity against a subset of clinical strains by microdilution revealed minimum inhibitory concentration and minimum bactericidal concentration ranging from 8 µg/mL to 64 µg/mL. The peptide was active against multidrug-resistant isolates with a bactericidal effect. Of note, despite numerous attempts, it proved impossible to select Campylobacter spp. for resistance to the brevibacillin Thr1 analog. These results underline the potential of lipopeptides, notably brevibacillin, as antimicrobial alternatives against antibiotic-resistant Campylobacter bacterial infections. Full article
(This article belongs to the Special Issue Antibacterial Activity against Drug-Resistant Strains, 2nd Edition)
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23 pages, 6139 KiB  
Article
Efficacy of Three Doses of Halquinol on Growth Performance, Diarrhea Incidence, Nutrient Digestibility, and Fecal Microbiome of Weaned Pigs
by Panumas Kongpanna, Uttra Jamikorn, Thitima Tripipat, Angkana Tantituvanont, Rakthai Ngampak and Dachrit Nilubol
Animals 2025, 15(9), 1258; https://doi.org/10.3390/ani15091258 - 29 Apr 2025
Viewed by 781
Abstract
The weaning period is a critical phase for nursery pigs that is characterized by rapid growth and alterations in the intestinal microbiome associated with nutrient utilization. The present study aimed to investigate the efficacy of halquinol, when used as an antibiotic (ABO), on [...] Read more.
The weaning period is a critical phase for nursery pigs that is characterized by rapid growth and alterations in the intestinal microbiome associated with nutrient utilization. The present study aimed to investigate the efficacy of halquinol, when used as an antibiotic (ABO), on the growth performance, diarrhea incidence, coefficient of apparent total tract digestibility (CATTD), fecal volatile fatty acids (VFAs), and microbiota in pigs. A total of 210 healthy weaned pigs with an average initial weight of 6.9 kg and aged 28 ± 2 days were assigned to five treatments (six pens/treatment) in a complete randomized design, including a control group (T1, CON; feed with no ABO), a colistin group (T2, CLT; feed containing 120 ppm colistin), and three halquinol groups (T3 to T5, HAL; feed containing 180, 240, and 360 ppm halquinol, respectively). The experiment period lasted for 10 days. Field recordings, observation, and feces collection were performed on D1, D5, and D10. CATTD and VFA assessments were conducted on D10. The composition of the fecal microbiota was analyzed via 16S rRNA gene sequencing using the Illumina Miseq platform. The results demonstrated that the in-feed ABO groups exhibited a significantly lower ADFI (p < 0.01). Pigs fed the T3 and T4 diets had the lowest FCR (p < 0.01) on D5 and D10 and, thus, had reduced ADFI (p < 0.01). A quadratic contrast was found in ADFI and FCR on D5 and D10, indicating a negative correlation with HAL concentration (p < 0.01). Pigs fed CLT and HAL had significantly reduced levels of coliform (p < 0.01) and E. coli (p < 0.01). Moreover, pigs receiving ABO also had a lower fecal score compared to those on the CON diet (p < 0.01). Dietary in-feed ABO had no effect on all the parameters of the CATTD on D10 (p > 0.05), except for fat digestibility in pigs that received T4 (p < 0.01). Pigs fed the T4 and T5 diets had higher propionate concentrations and lower A/P ratios than pigs fed T1, T2, and T3 (p < 0.01). The microbial diversity shifted quickly through the early weaning period. The relative abundance of beneficial Enterococcus microbes increased in pigs fed in-feed ABO, whereas the relative prevalence of pathogenic bacteria, such as Escherichia and Klebsiella, decreased. Escherichia and Bacteroides were negatively correlated with carbohydrate digestibility and butyric and valeric acid production (p < 0.05). Overall, the appropriate HAL dosage was 240 ppm (T4), and this antimicrobial can potentially be characterized as an in-feed colistin replacer that improves feed efficiency and fat digestion, enhancing VFA production, alleviating post-weaning diarrhea, and protecting ABO-resistant piglets. Full article
(This article belongs to the Section Animal Nutrition)
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16 pages, 3392 KiB  
Article
Inhibitory Effects of Phellodendri Cortex Against Airway Inflammation and Hyperresponsiveness in Ovalbumin-Induced Murine Asthma Model
by Seong-Kyeom Kim, Ji-Won Do, Seong-Kyun Lee, Jae-Ho Park, Ju-Hyoung Kim and Heung-Bin Lim
Molecules 2025, 30(8), 1795; https://doi.org/10.3390/molecules30081795 - 16 Apr 2025
Viewed by 947
Abstract
Phellodendri cortex (PC), the dried trunk bark of Phellodendron amurense RUPR, has traditionally been used to treat patients who suffer from gastroenteritis, abdominal pain or diarrhea. Its major bioactive compounds include alkaloids and limonin, and many physiological activities including anti-microbial, anti-ulcer and anti-cancer [...] Read more.
Phellodendri cortex (PC), the dried trunk bark of Phellodendron amurense RUPR, has traditionally been used to treat patients who suffer from gastroenteritis, abdominal pain or diarrhea. Its major bioactive compounds include alkaloids and limonin, and many physiological activities including anti-microbial, anti-ulcer and anti-cancer as well as anti-inflammation have been reported. Although PC is an effective anti-inflammatory natural substance that inhibits the inflammatory response, its effect on allergic asthma has not yet been investigated. The aim of this study was to evaluate the anti-asthmatic effects of PC in an ovalbumin (OVA)-induced murine model of asthma. As a result, PC inhibited airway eosinophil accumulation, the influx of inflammatory cells, airway hyperresponsiveness (AHR), production of Th2 cytokines (IL-4, IL-5 and IL-13) and tumor necrosis factor-α (TNF-α) in the bronchoalveolar lavage fluid and/or lung, as well as OVA-specific immunoglobulin E (IgE) in the serum. Furthermore, PC suppressed the gene expression of IL-4, IL-5, IL-13, TARC and CCR3, and attenuated unique histological changes that are associated with airway inflammatory reactions including the infiltration of various inflammatory cells, collagen deposition and goblet cell hyperplasia in lung tissues. These results indicate that PC may have preventive and/or therapeutic effects for allergic asthma via the inhibition of cytokines, chemokines and chemokine receptors associated with allergic inflammation. Full article
(This article belongs to the Section Natural Products Chemistry)
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25 pages, 5923 KiB  
Review
Deciphering the Structural and Functional Paradigms of Clostridioides difficile Toxins TcdA and TcdB
by Mohammad Qutub, Amol Tatode, Ujban Md Hussain, Tanvi Premchandani, Jayshree Taksande, Milind Umekar and Deepak Thakre
Bacteria 2025, 4(2), 21; https://doi.org/10.3390/bacteria4020021 - 3 Apr 2025
Cited by 1 | Viewed by 1739
Abstract
Clostridioides difficile Infection (CDI) continues to be a major cause of antibiotic-associated diarrhea and pseudomembranous colitis, fueled in large measure by virulence factors TcdA and TcdB. These giant glucosyltransferase toxins interfere with host cytoskeletal integrity and inflammatory signaling by inhibiting Rho GTPase; however, [...] Read more.
Clostridioides difficile Infection (CDI) continues to be a major cause of antibiotic-associated diarrhea and pseudomembranous colitis, fueled in large measure by virulence factors TcdA and TcdB. These giant glucosyltransferase toxins interfere with host cytoskeletal integrity and inflammatory signaling by inhibiting Rho GTPase; however, the detailed structural dynamics, receptor selectivity, and subcellular trafficking mechanisms remain in part unspecified. This review integrates recent insights from cryo-electron microscopy (cryo-EM) and X-ray crystallography to describe the quaternary architecture of TcdA/B, emphasizing conformational changes key to pore formation and endosomal escape. We also examine the genomic heterogeneity of hypervirulent C. difficile strains (e.g., ribotype 027), correlating toxin gene polymorphisms (e.g., tcdC mutations) with increased toxin production and virulence. Mechanistic explanations of toxin-driven inflammasome activation and epithelial barrier dysfunction are situated within host immune evasion mechanisms, including microbiota-derived bile acid regulation of toxin stability. Subsequent innovative therapeutic strategies, encompassing the utilization of engineered neutralizing antibodies that specifically target the autoprocessing domain alongside structure-guided small-molecule inhibitors, are subjected to a rigorous evaluation. By integrating structural biology, systems-level omics, and clinical epidemiology, this review establishes a comprehensive framework for understanding C. difficile toxin pathogenesis and guiding next-generation precision antimicrobials. Full article
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16 pages, 692 KiB  
Review
The Role of Clostridioides difficile Within the One Health Framework: A Review
by Sotiris Alexiou, Anastasia Diakou and Melania Kachrimanidou
Microorganisms 2025, 13(2), 429; https://doi.org/10.3390/microorganisms13020429 - 16 Feb 2025
Cited by 3 | Viewed by 1359
Abstract
Clostridioides difficile is the leading cause of antibiotic-associated diarrhea in hospitalized patients. In recent years, the incidence of C. difficile infection (CDI) has increased globally, with a notable rise in community-associated CDI (CA-CDI). The presence of the microorganism in animals, the environment, and [...] Read more.
Clostridioides difficile is the leading cause of antibiotic-associated diarrhea in hospitalized patients. In recent years, the incidence of C. difficile infection (CDI) has increased globally, with a notable rise in community-associated CDI (CA-CDI). The presence of the microorganism in animals, the environment, and food suggests that these sources may contribute to the spread of the infection in the community. This review applies a One Health approach, integrating human, animal, and environmental health, to provide a comprehensive strategy for understanding and managing this pathogen. Findings reveal the widespread dissemination of C. difficile in animals, the environment, and food. The predominant PCR ribotypes identified were RTs 078 and 014/020, followed by RTs 126, 001, 002, 009, 010, and 033. C. difficile strains exhibited resistance to multiple antimicrobial agents, including clindamycin, erythromycin, fluoroquinolones, cephalosporins, and tetracyclines. Discriminative typing methods, such as whole-genome sequencing, revealed clonal relationships between C. difficile strains from humans and animals, indicating either direct transmission or a common environmental source of infection. The high genetic similarity between isolates from the environment and humans indicates potential environmental contamination. Additionally, clusters of C. difficile strains found in food and humans indicate a possible foodborne transmission route. This review summarizes the current knowledge on the role of Clostridioides difficile within the One Health framework. Full article
(This article belongs to the Section Medical Microbiology)
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24 pages, 3281 KiB  
Review
Cranberry: A Promising Natural Product for Animal Health and Performance
by Sahdeo Prasad, Bhaumik Patel, Prafulla Kumar, Pranabendu Mitra and Rajiv Lall
Curr. Issues Mol. Biol. 2025, 47(2), 80; https://doi.org/10.3390/cimb47020080 - 27 Jan 2025
Cited by 1 | Viewed by 3720
Abstract
Cranberries are a distinctive source of bioactive compounds, containing polyphenols such as flavonoids, anthocyanins, phenolic acids, and triterpenoids. Cranberries are often associated with potential health benefits for the urinary tract and digestive system due to their high antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. [...] Read more.
Cranberries are a distinctive source of bioactive compounds, containing polyphenols such as flavonoids, anthocyanins, phenolic acids, and triterpenoids. Cranberries are often associated with potential health benefits for the urinary tract and digestive system due to their high antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Cranberry induces the production of antioxidant enzymes, suppresses lipid peroxidation, reduces inflammatory cytokines, modulates immune cells, maintains gut microbiota, and inhibits bacterial adhesion and growth. Cranberry polyphenols also have metal-binding motifs that bind with metals, particularly zinc and iron. The combination of cranberry polyphenols and metals displays increased biological activity. In this review, an attempt is made to describe the physiological properties and health benefits of cranberries for livestock, including poultry, swine, canine, feline, and ruminant animals, as either feed/food or as supplements. Cranberry, and/or its components, has the capability to potentially control infectious diseases like diarrhea, urinary tract infection, gut integrity, and intestinal probiotic health. Moreover, cranberries show efficacy in suppressing the growth of pathogenic microorganisms such as Salmonella species, Campylobacter species, Streptococcus species, and Enterococcus species bacteria. Thus, cranberry could be considered as a potential natural feed additive or food supplement for animal health improvement. Full article
(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)
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29 pages, 2179 KiB  
Review
Bovine Colostrum in Pediatric Nutrition and Health
by Ahmet Alperen Canbolat, Mauro Lombardo, Alicia del Carmen Mondragon, Jose Manuel Miranda López, Mikhael Bechelany and Sercan Karav
Nutrients 2024, 16(24), 4305; https://doi.org/10.3390/nu16244305 - 13 Dec 2024
Cited by 1 | Viewed by 4552
Abstract
Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets [...] Read more.
Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets and support development. Preterm development is crucial, especially in the maturation of essential systems, and from 2010 to 2020, approximately 15% of all premature births occurred at less than 32 weeks of gestation worldwide. This review explores the composition, benefits, and effects of BC on general infants and children, along with preterm infants who require special care, and highlights its role in growth and development. BC is also associated with specific pediatric diseases, including necrotizing enterocolitis (NEC), infectious diarrhea, inflammatory bowel disease (IBD), short-bowel syndrome (SBS), neonatal sepsis, gastrointestinal and respiratory infections, and some minor conditions. This review also discusses the clinical trials regarding these specific conditions which are occasionally encountered in preterm infants. The anti-inflammatory, antimicrobial, immunomodulatory, and antiviral properties of BC are discussed, emphasizing its mechanisms of action. Clinical trials, particularly in humans, provide evidence supporting the inclusion of BC in formulas and diets, although precise standards for age, feeding time, and amounts are needed to ensure safety and efficacy. However, potential adverse effects, such as allergic reactions to caseins and immunoglobulin E, must be considered. More comprehensive clinical trials are necessary to expand the evidence on BC in infant feeding, and glycans, important components of BC, should be further studied for their synergistic effects on pediatric diseases. Ultimately, BC shows promise for pediatric health and should be incorporated into nutritional supplements with caution. Full article
(This article belongs to the Special Issue Advances in Infant and Pediatric Feeding and Nutrition)
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7 pages, 551 KiB  
Case Report
Integrating Diagnostic Approaches in Infant Bacterial Meningitis Caused by a Non-K1 Escherichia coli: A Case Report
by Gianluca Vrenna, Marilena Agosta, Valeria Fox, Martina Rossitto, Venere Cortazzo, Serena Raimondi, Barbara Lucignano, Manuela Onori, Livia Mancinelli, Maria del Carmen Pereyra Boza, Vanessa Fini, Annarita Granaglia, Laura Lancella, Francesca Ippolita Calo’ Carducci, Costanza Tripiciano, Alberto Villani, Paola Bernaschi and Carlo Federico Perno
Antibiotics 2024, 13(12), 1144; https://doi.org/10.3390/antibiotics13121144 - 28 Nov 2024
Cited by 1 | Viewed by 1302
Abstract
Background: Infant meningitis, particularly caused by Escherichia coli, remains a life-threatening condition, especially in premature and low-weight infants. Infections of the central nervous system can be fatal, necessitating prompt diagnosis and appropriate treatment. Acute infections caused by various pathogens, including E. coli [...] Read more.
Background: Infant meningitis, particularly caused by Escherichia coli, remains a life-threatening condition, especially in premature and low-weight infants. Infections of the central nervous system can be fatal, necessitating prompt diagnosis and appropriate treatment. Acute infections caused by various pathogens, including E. coli, often present with similar clinical symptoms. The rapid identification of pathogens and their antimicrobial resistance mechanisms is critical for timely and effective treatment. We report the case of an 8-month-old patient who presented with fever, diarrhea, and convulsive seizures and was subsequently diagnosed with meningitis. Despite initial empirical treatment with ceftriaxone, the patient’s condition worsened. Methods: At Bambino Gesù Children’s Hospital, molecular diagnostic tools, including the FilmArray Meningitis/Encephalitis and Blood Culture Identification panels, were employed. Results: Although the Meningitis panel did not detect any pathogens due to the lack of the specific bacterial target, the off-label use of the Blood Culture Identification panel identified a non-K1 Escherichia coli strain carrying the CTX-M resistance gene, an extended-spectrum beta-lactamase (ESBL). Despite the rapid diagnostic approach and adjustment of antibiotic therapy, the patient succumbed to the infection due to the strain’s high virulence and multidrug resistance. Whole-genome sequencing further characterized the strain, revealing that it belonged to the ST131 group, a highly resistant and virulent strain associated with sepsis. Conclusions: This case highlights the importance of integrating advanced molecular diagnostics, such as whole-genome sequencing, with traditional methods to improve pathogen detection, especially in cases of emerging resistant strains that are not covered by standard diagnostic panels. It also emphasizes the need for the continuous adaptation of diagnostic tools to include non-K1 E. coli strains for more comprehensive and timely meningitis diagnosis. Full article
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