Search Results (6,105)

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

Background: The gut microbiome is crucial in sustaining intestinal balance and general health. Following rectal cancer surgery, the creation of a diverting stoma to protect the anastomosis results in a defunctioned colon, leading to dysbiosis. The effect of probiotic intake on gut dysbiosis following ileostomy repair remains uncertain. Thus, this study aims to determine the changes in gut microbiota based on the intake of probiotics after diverting stoma repair. Methods: This single-center, parallel, prospective pilot study will include patients with primary rectal cancer planning to undergo a diverting stoma during rectal cancer surgery. The study will comprise 20 patients, with 10 patients receiving synbiotics after stoma repair and 10 patients not receiving probiotics. The primary endpoint is the change in the gut microbiota of the resting colon based on the intake of probiotics, assessed through fecal testing at the following time points: before bowel resection, immediately after diverting stoma repair, and 3 weeks after diverting stoma repair. Changes in gut microbiota will be evaluated using alpha- and beta-diversity analyses based on 16S rRNA sequencing of fecal samples. Discussion: This study is the first prospective cohort trial investigating changes in the gut microbiota of the resting colon based on oral probiotic administration in patients undergoing diverting stoma repair. This trial is anticipated to clarify the impact of probiotic intake in these patients. Trial registration: Clinical Research Information Service (CRIS) of the Republic of Korea, KCT0008392, Registered on 27 April 2023. Full article

Background/Objectives: This study investigated how phase-specific dietary strategies and weight regulation influence gut microbiota composition and diversity in competitive weightlifters. Particular emphasis was placed on integrating energy intake, macronutrient clustering, and weight fluctuations across distinct training phases. Methods: Thirteen competitive weightlifters were recruited, with 10–12 contributing complete data per phase. Fecal and dietary samples were collected during the preparation, competition, and transition phases. Gut microbiota was profiled via 16S rRNA gene sequencing, and alpha/beta diversity was analyzed using QIIME2. K-means clustering based on caloric/macronutrient intake identified dietary patterns. Taxonomic differences were assessed using DESeq2, and microbial structures were compared across training phases, weight classes, and weight-change categories. Results: Overall phylum- and genus-level profiles and diversity indices remained stable across training phases, indicating community-level resilience. However, specific genera varied with dietary and physiological factors. Enterococcus was higher during the preparation phase, whereas Lactobacillus was enriched during the competition and transition phases as well as in the high-calorie cluster. Lightweight and heavyweight athletes also showed distinct microbial structures, and pre- and post-competition weight changes were associated with shifts in selected taxa. Notably, the low-calorie group exhibited higher Shannon diversity than the high-calorie group (p = 0.0058), with Lactobacillus dominance contributing to reduced evenness in high-energy diets. Conclusions: Despite overall microbial stability, dietary energy availability and body-weight regulation modulated specific taxa relevant to performance and recovery. By integrating dietary clustering, weight-class comparison, and pre- and post-competition weight changes, this study provides novel insight into the microbiota of resistance-trained athletes, a population underrepresented in previous research. Despite the modest sample size and single-season scope, this study offers new evidence linking dietary strategies, weight regulation, and gut microbiota in weightlifters, and highlights the need for validation in broader cohorts. Full article

Background: Periodontitis is a chronic disease triggered by disturbed oral microbiota. We have previously reported that hepatocyte growth factor (HGF) could mitigate early-stage experimental periodontitis but exacerbate the condition in its late stage. Here, we investigated the impact of HGF on the periodontal microbiome during periodontitis progression. Methods: We established ligation-induced periodontitis in wild-type (WT) mice and HGF high-expression transgenic (HGF-Tg) mice. We quantified the levels of IL-6 and TNF-α in periodontal tissues, as well as the serum concentrations of CTXI and PINP. Ligatures were collected on days 0, 7, and 28 after ligation for 16S rRNA sequencing and microbial analysis. Results: HGF significantly altered the diversity of ligatures during periodontitis. Interestingly, specific microbial genera, such as Lactobacillus, exhibited opposing trends between the two disease stages of HGF-Tg mice, aligning with the different effects of HGF on periodontitis progression. We also identified some taxa, such as Sphingomonas, associated with IL-6, TNF-α, CTXI, and PINP. The predicted inflammatory pathways (e.g., IL-17 signaling pathways) were enriched in HGF-Tg mice on day 28 but decreased on day 7. Conclusions: HGF exerted different influences on the microbiota of ligatures during early and late stages of periodontitis, which may account for the divergent effects of HGF on periodontitis progression. Full article

Background/Objectives: Osteoporosis is a prevalent and debilitating skeletal disease characterized by a progressive loss of bone mass and deterioration of bone microarchitecture. Probiotics have emerged as a potential therapeutic tool for treating osteoporosis through modulation of the gut microbiota. In this study, we aimed to examine the effects of live Lacticaseibacillus rhamnosus AC1 (LR-AC1), isolated from a fecal sample from a newborn in Hong Kong, on deoxycorticosterone acetate (DOCA)-induced bone loss in a rat model. Methods: Bone mass and microarchitecture were assessed using micro-computed tomography (micro-CT). Immunostaining for CD31⁺ and osterix, markers of endothelial cells and osteoblast precursors, respectively, was performed. Gut microbiota composition was analyzed via 16S rRNA sequencing. The effects of an LR-AC1 cell-free conditioned supernatant (CCS) on osteoclastogenesis, angiogenesis, and migration of bone marrow mesenchymal stem cells (BMSCs) were evaluated in vitro using RT-qPCR and wound healing assays. Results: LR-AC1 administration did not induce adverse effects in healthy rats; however, it exacerbated bone loss in rats with DOCA-salt-induced osteoporosis. Correspondingly, the number of CD31-positive endothelial cells and osterix-positive osteoprogenitors decreased with bone loss. In vitro, LR-AC1 CCS promoted osteoclastogenesis and angiogenesis, while in the presence of DOCA, LR-AC1 CCS inhibited BMSC migration. Gut microbiota analysis revealed that the relative abundances of the genera g_RF39 and g_Clostridia_UCG-014 correlated with the severity of bone loss. Conclusions: While several studies suggest that probiotics can prevent and treat osteoporosis, our findings indicate that in a male rat model of DOCA-salt-induced osteoporosis, live LR-AC1 aggravated bone loss. This effect is associated with alterations in gut microbiota and disruption of the coupling process in bone remodeling. Full article

Caries is the most prevalent chronic disease affecting oral health in preschool children. In this 12-month prospective cohort study of 3–4-year-olds, we investigated the community-level bacterial–fungal interkingdom interactome and its role in cariogenic microenvironments, using 16S rRNA gene (bacterial) sequencing and ITS2 gene (fungal) sequencing of unstimulated saliva. Longitudinal analysis identified 19 key bacterial and fungal species that were associated with both caries progression and clinical features. Salivary bacteria Desulfovibrio, Bacteroides heparinolyticus, Alloprevotella, Anaerobiospirillum, and fungus Candida tropicalis not only showed altered abundances during caries development but also correlated with severity of caries, establishing diagnostic microbial signatures for caries prediction. The salivary mycobiome exhibited highly active and complex intra-network interactions in the caries-active state, suggesting that fungal networks may drive the broader community-wide microbiota interaction network in the caries state. Metabolic profiling further revealed distinct pathway shifts before and after caries onset. The findings demonstrate that caries progression follows ecological succession governed by cross-domain interactions. This study highlighted the fungal network’s important role in driving dysbiosis, advancing the current understanding of early childhood caries beyond bacterial-centric models, and also highlighted fungi not only as modulators but as active contributors to cariogenesis, which could guide future antimicrobial strategies. Full article

The increasing reliance on imported fish products in Kazakhstan raises concerns about the presence of fish-borne parasitic infections, particularly zoonotic helminths that pose risks to public health. This study aimed to assess the diversity and prevalence of helminths in commercially imported marine fish using both traditional and molecular diagnostic methods. A total of 670 specimens representing 17 fish species were collected from retail markets in Astana, Almaty, and Karaganda. Macroscopic inspection and muscle compression techniques were used to detect larval parasites, followed by DNA extraction and PCR amplification targeting the ITS-2, 5.8S, 18S rRNA, and mitochondrial COX gene regions. Sequencing and phylogenetic analysis confirmed the presence of cestodes (Eubothrium crassum, Hepatoxylon trichiuri, Nybelinia surmenicola), acanthocephalans (Echinorhynchus gadi), and nematodes, with a predominance of zoonotic species from the Anisakidae family, including Anisakis simplex, A. pegreffii, Pseudoterranova decipiens, and Contracaecum osculatum. The highest levels of infection were detected in Atka mackerel (97.1%), herring (96.0%), mackerel (92.0%), and blue whiting (88.1%), while the lowest rates were recorded in smelt (6.8%), flounder (10.2%), and haddock (16.0%). This is the first molecular-based survey of fish helminths in Kazakhstan and highlights the need to integrate genetic screening into food safety control systems to better protect consumers and improve parasite monitoring of imported seafood. Full article

The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown adipocytes via a comparative analysis using typical mouse brown adipose tissue sections. We found that swine brown adipocytes were distributed in an island-like pattern, with three typical characteristics: (1) numerous mitochondria and small lipid droplets, (2) a cellular volume smaller than that of white adipocytes, and (3) expression of specific marker genes (EBF2 and ATP2B4). The expression levels of the thermogenesis-related genes UCP2/3 were not significantly increased. Thus, we conducted ceRNA network analysis, revealing that high expression of the key microRNA miR-10383 increased the thermogenic efficiency of UCP3 in the cold exposure group. In addition, the epigenetic memory of UCP3 was disrupted. Chromatin accessibility and Whole-Transcriptome Sequencing of Groin Adiposesibility results revealed peaks in the promoter regions of the UCP2/3 genes. In our discussion of the study’s limitations, we explain how to repeat the experiment to significantly increase the UCP2/3 protein content. This study fills a research gap regarding brown fat in pigs and can provide a reference for future studies on fat metabolism. Full article

Intestinal bacterial dysbiosis develops in a number of immune-mediated disorders. Fecal microbiota transfer (FMT) is considered a potentially efficient tool for restoration of the patient’s gut microbiota. The aim of our study was to trace the time course of dominant bacterial populations and some Enterobacteria phages in patients with GVHD and Crohn’s disease after FMT procedure. Patients and methods: We observed 12 patients with intestinal graft-versus-host disease (GVHD), and 15 persons with Crohn’s disease after massive anti-infectious treatment. FMT was performed by a standard protocol using oral capsules administered for 2 days. Fecal bacteriome was assessed by 16S rRNA sequencing. Viral sequences were identified by NGS with a customized primer set. Plasma citrulline levels were measured in order to assess enterocyte damage in the patients. Results: Complete clinical response to FMT was observed in 5 of 12 GVHD patients and 10 of 15 Crohn’s disease cases. Before FMT, most anaerobic Bacillota were exhausted in both Crohn’s disease patients and GVHD. Following FMT, Akkermansia ratios tended to decrease within 30 days in Crohn’s disease, along with higher Faecalibacteria, Romboutsia, and Dialister ratios than in GVHD, thus suggesting lesser damage to anaerobic microbiota in Crohn’s disease. Increased contents of facultative anaerobes (Enterococcus and E. coli) was detected in GVHD patients after FMT. Fecal virome changes in Crohn’s disease after FMT included early transient decrease in Caudoviricetes with a rise in Lederbergvirus and Eganvirus ratios at later terms. In GVHD patients, reverse correlations were revealed between E. coli and E. coli-hosted Eganvirus species. Intestinal damage assessed by low plasma citrulline levels was associated with fecal Klebsiella expansion, being more pronounced in GVHD than in Crohn’s disease. Clinical response to FMT in GVHD patients correlated with increased plasma citrulline and lower Eganvirus abundance. Future studies will concern specific relations between fecal bacteriome and virome reconstitution following FMT in gut GVHD and other immune-mediated intestinal disorders. Full article

The gut microbiota of insects, shaped by extensive coevolution, plays a crucial role in host adaptability and ecological expansion. The fall armyworm (Spodoptera frugiperda J.E. Smith), a highly polyphagous and migratory invasive pest, infests more than 350 plant species worldwide, resulting in substantial crop losses and increased reliance on pesticide applications. In this study, we employed 16S rRNA high-throughput sequencing to investigate diet-induced alternations in the gut microbial communities of larvae fed corn, rice, or an artificial diet. The results showed that diet significantly influenced microbial diversity, with rice-fed larvae exhibiting the highest richness. Firmicutes, Proteobacteria, and Cyanobacteria were the predominant bacterial phyla. Genus-level analysis revealed notable diet-dependent shifts, with Enterobacter and other genera (e.g., Ochrobactrum and Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium) only detected in plant-fed groups. Additionally, current findings suggest that gut microbial genera are more prevalent when S. frugiperda larvae feed on rice plants than on corn plants or an artificial diet and are closely linked to their metabolic activities. Dominant microbial genera are expected to support essential metabolic processes and exhibit increased abundance on rice. These results indicate that the gut microbiome of S. frugiperda is diet-driven reorganization, potentially facilitating its polyphagy. This study extends the current understanding by elucidating the specific gut microbial taxa and their putative metabolic associations that are responsive to diet in S. frugiperda, thereby providing a theoretical basis for its polyphagous capability and underscoring microbiota-based strategies for sustainable pest management. Full article

Background: Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited. Eupatorium lindleyanum DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear. Objective: This study aimed to evaluate the protective effects of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques. Results: SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL’s pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota–metabolite–inflammatory cytokine network, thereby maintaining gut–lung axis homeostasis and enhancing anti-inflammatory effects. Conclusions: SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut–lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI. Full article

In May 2025, a female giraffe in poor body condition died unexpectedly at a zoo in Henan Province, China. A bacterial strain, designated HN-1, was isolated from the heart, liver, spleen, lungs, and kidneys of the deceased animal. After 24 h of incubation at 37 °C on Luria–Bertani (LB) agar, the colonies appeared round, smooth, pale yellow, translucent, and raised. Gram staining revealed that the isolate was a Gram-positive, rod-shaped, and non-spore-forming bacterium. Based on 16S rRNA gene sequencing, the strain showed more than 99.7% homology with reference sequences of E. mexicanum from various sources in GenBank. The results of the susceptibility test showed that E. mexicanum was susceptible to levofloxacin, clindamycin, chloramphenicol, trimethoprim, rifampicin, tetracycline, minocycline, gentamicin, erythromycin, and doxycycline, but resistant to oxacillin, penicillin, ciprofloxacin, and linezolid. These findings provide valuable insights for the diagnosis and treatment of infections caused by E. mexicanum in giraffes. Full article

Lower respiratory tract infections (LRTIs) represent a significant global health concern, and the accurate identification of pathogens is crucial for patient care. Culture-based methods are the gold standard, but their detection abilities are limited. Next-generation sequencing (NGS) offers a promising method for comprehensive microbial detection, providing valuable information for clinical practice. In this study, 144 bronchoalveolar lavage fluid samples were collected, culture-based diagnostics were performed, and bacterial microbiome profiles were generated by short-read sequencing of the V4 region of the 16S rRNA gene using Illumina technologies and long-read sequencing with Oxford Nanopore Technologies (ONT) to determine the full-length 16S rRNA gene. The most common genera detected by NGS included Streptococcus, Staphylococcus, Veillonella, Prevotella, Rothia, Enterococcus, and Haemophilus. Short-read sequencing detected cultured bacteria at the genus level in ~85% of cases, while long-read sequencing demonstrated agreement with cultured species in ~62% of cases. In three cases, long-read sequencing identified the uncommon potential lung pathogen Tropheryma whipplei not detected with traditional culturing techniques. The NGS results showed a partial overlap with culture as the current diagnostic gold standard in LRTI. Additionally, NGS detected a broader spectrum of bacteria, revealed fastidious potential pathogens, and offered deeper insights into the complex microbial ecosystem of the lungs. Full article

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive pest in tea plantations, leading to significant economic losses through defoliation. Existing control strategies, including chemical insecticides and biological agents, are often limited by environmental concerns, resistance, and variable efficacy. Recent evidence suggests that bacteria influence insect physiology and could be leveraged for pest management, but the postmortem microbial ecology of E. grisescens remains uncharacterized. In this study, we employed 16S rRNA sequencing to investigate temporal changes in the bacterial communities of E. grisescens cadavers at 0, 7, and 21 days following cryogenic mortality. Our results indicate a time-dependent decline in microbial diversity, while species richness initially increased before subsequent reduction. The dominant endosymbiont Wolbachia gradually diminished after host death, whereas Enterobacter remained abundant. Notably, non-dominant genera including Lysinibacillus and Sporosarcina exhibited a transient increase in abundance at day 7 before reverting to control levels by day 21. This study presents the first comprehensive analysis of postmortem microbial succession in a lepidopteran system, highlighting dynamic shifts in bacterial composition and offering potential avenues for microbiome-based pest management strategies. Full article

Background/Objectives: Dysbiosis of the vaginal microbiota, particularly the loss of Lactobacillus spp. dominance, is linked to female infertility. While community state types (CSTs) I–III and V have been studied extensively, CST IV remains underexplored. The aim of this prospective study was to compare vaginal microbiota composition—specifically CST IVA and IVB—between fertile and infertile women. Methods: Vaginal samples were collected from 22 women (15 infertile, 7 fertile) using cervical brushes and analyzed via 16S rRNA gene sequencing. DNA was extracted, and V3–V4 regions were sequenced using the Illumina MiSeq platform. Taxonomic classification was performed with QIIME 2 and the Greengenes database. Differences in microbial composition were assessed using the Wilcoxon rank-sum test (p < 0.05) in SPSS v21.0. Results: Infertile women showed lower relative abundances of Lactobacillus spp. (31.54% vs. 42.32%) and Oscillospira spp. relative to fertile women. CST IV was more frequent in the infertile group (29.75% vs. 21.61%). Within CST IV, CST IVA accounted for a higher proportion in infertile women (7.0% vs. 0.94%), with Prevotella spp. representing 95.18% of CST IVA in infertile subjects, as opposed to the figure of 69.77% in fertile counterparts. No clear differences in CST IVB were observed between groups. Conclusions: Increased prevalence of Prevotella spp. in CST IVA may contribute to an unfavorable vaginal environment in infertile women, potentially affecting sperm viability. The presence of Oscillospira spp. in fertile women suggests it is associated with a healthy vaginal microbiota profile. Full article