Gut Barrier Dysfunction: Mechanisms, Implications, and Treatment Strategies for Enhancing Animals Production

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: 30 June 2025 | Viewed by 4611

Special Issue Editors


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Guest Editor
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
Interests: gut microbiota; omics; proteomics

E-Mail Website
Guest Editor
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
Interests: apoptosis; inflammasome; poultry; probiotics; cell culture; metabolomic profile; 16s rRNA sequencing
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Special Issue Information

Dear Colleagues,

This current Special Issue brings together innovative research and comprehensive reviews that explain the complicated interaction of gut barrier dysfunction in animal health. Given the prime role of an intestinal barrier in general health, its destruction will compromise animals, leading to them being more susceptible to diseases as a result of the weakening of the immune responses toward a higher risk of systemic infection. This present Special Issue discusses the myriad of multifactorial causes in disrupting gut barriers in both livestock and companion animals, and hence will be tackling environmental stressors, dietary factors, microbial dysbiosis, genetic susceptibilities, molecular mechanisms supporting gut integrity, recent developments in diagnostic indicators, and nutrition and probiotics effects on gut health restoration. Furthermore, the current study aims to investigate the contribution of gut barrier integrity to the immune response and its interaction with the susceptibility of animals to infection, especially under the conditions of intensive husbandry. Submissions dealing with new therapeutic approaches, such as nutritional supplementation, microbial intervention, and pharmacological intervention, are also invited.

This Issue aims to enhance the understanding of gut barrier function by integrating different disciplines' studies and stimulating new manners of tackling health problems due to barrier dysfunction within animal groups.

Dr. Kun Li
Dr. Mo Quan
Dr. Md. F. Kulyar
Guest Editors

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Keywords

  • gut barrier dysfunction
  • animal health
  • immune response
  • microbial dysbiosis
  • nutritional and therapeutic interventions

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Published Papers (5 papers)

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Research

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15 pages, 2415 KiB  
Article
Effects of Phytogenic Feed Additive on Production Performance, Slaughtering Performance, Meat Quality, and Intestinal Flora of White-Feathered Broilers
by Jianming Ren, Siyu Ren, Haochi Yang and Peng Ji
Vet. Sci. 2025, 12(5), 396; https://doi.org/10.3390/vetsci12050396 - 22 Apr 2025
Viewed by 270
Abstract
This study systematically evaluates the effects of dietary supplementation with phytogenic feed additive (0.2%, 0.4%, and 0.8%) on white-feathered broilers (n = 88) through a 42-day controlled trial with the weight of approximately 50 g. The experimental design incorporates a triplicate-group-replicated protocol with [...] Read more.
This study systematically evaluates the effects of dietary supplementation with phytogenic feed additive (0.2%, 0.4%, and 0.8%) on white-feathered broilers (n = 88) through a 42-day controlled trial with the weight of approximately 50 g. The experimental design incorporates a triplicate-group-replicated protocol with daily feed intake monitoring, culminating in comprehensive assessments of the growth performance, slaughter traits, meat quality, and cecal microbiome dynamics. The results demonstrated that the 0.8% supplementation significantly enhanced average daily weight gain (p < 0.05), optimized meat characteristics (elevated the redness of meat, reduced pH; p < 0.05), and restructured cecal microbiota by enriching Deinococcus-Thermus, Bacteroidetes, Actinobacteria, and Cyanobacteria (p < 0.05). Based on microbiota-based functional prediction analyses (COG/KEGG/MetaCyc), phytogenic feed additive significantly activated lipid metabolism pathways in broilers. The immunomodulatory correlations between Deinococcus/Thermus/Cyanobacteria and immune indicators suggested their potential immune-enhancing effects mediated through host immune regulation. The findings established the 0.8% phytogenic feed additive as a multifunctional phytogenic additive that synchronously improves zootechnical performance, meat quality, and microbiome homeostasis, offering a scientifically validated strategy for antibiotic-free precision nutrition in sustainable poultry production. Full article
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18 pages, 10335 KiB  
Article
Cow Placenta Peptides Ameliorate D-Galactose-Induced Intestinal Barrier Damage by Regulating TLR/NF-κB Pathway
by Yuquan Zhao, Zhi Zeng, Weijian Zheng, Zeru Zhang, Hanwen Zhang, Yuxin Luo, Kunshan Zhao, Yuyan Ding, Wei Lu, Fuxing Hao, Yixin Huang and Liuhong Shen
Vet. Sci. 2025, 12(3), 229; https://doi.org/10.3390/vetsci12030229 - 3 Mar 2025
Viewed by 810
Abstract
This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group [...] Read more.
This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP’s effects, highlighting TLR4, IL-1β, and Mmp9 as core regulatory genes through protein–protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity. Full article
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15 pages, 3412 KiB  
Article
Epigallocatechin Gallate Alleviates Lipopolysaccharide-Induced Intestinal Inflammation in Wenchang Chicken by Inhibiting the TLR4/MyD88/NF-κB Signaling Pathway
by Xin Xu, Kunpeng Li, Qian Liu, Haiwen Zhang and Lianbin Li
Vet. Sci. 2025, 12(3), 225; https://doi.org/10.3390/vetsci12030225 - 2 Mar 2025
Viewed by 900
Abstract
Intestinal inflammation significantly compromises broiler health and adversely affects growth performance. Epigallocatechin gallate (EGCG) was found to maintain the gut health of animals. However, the role and mechanism of EGCG in preventing lipopolysaccharide (LPS)-induced intestinal inflammation in chicks have not yet been fully [...] Read more.
Intestinal inflammation significantly compromises broiler health and adversely affects growth performance. Epigallocatechin gallate (EGCG) was found to maintain the gut health of animals. However, the role and mechanism of EGCG in preventing lipopolysaccharide (LPS)-induced intestinal inflammation in chicks have not yet been fully elucidated. In the 35-day study, 140 one-day-old Wenchang chickens were randomly assigned to four treatments: CON (basal diet), LPS (basal diet + 1 mg/kg body weight (BW) LPS), L-EGCG (basal diet + 40 mg/kg BW EGCG + 1 mg/kg BW LPS), and H-EGCG (basal diet + 60 mg/kg BW EGCG + 1 mg/kg BW LPS). On days 31, 33, and 35 of age, broilers in the LPS, L-EGCG, and H-EGCG treatments received intraperitoneal injections of LPS. The LPS reduced jejunal villus height, villus height/crypt depth ratio, Claudin1 mRNA, catalase (CAT) activity, and interleukin-10 (IL-10) levels compared to CON while elevating diamine oxidase (DAO), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α). EGCG improved growth performance in LPS-challenged broilers, elevating jejunal villus height and Claudin1/ZO-1 mRNA with reduced serum DAO. It enhanced antioxidant capacity via increased serum total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), CAT, glutathione peroxidase (GSH-Px) activities, and a decreased malondialdehyde (MDA) concentration. Concurrently, EGCG lowered IL-1β/TNF-α and raised IL-10 in serum/jejunum. Crucially, EGCG suppressed jejunal TLR4/MyD88/NF-κB mRNA and protein expression under LPS. These findings demonstrate EGCG’s protective role against LPS-induced intestinal inflammation in Wenchang chickens through TLR4/MyD88/NF-κB pathway inhibition. Full article
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24 pages, 16741 KiB  
Article
Evaluating the Effect of Dietary Protein–Energy Ratios on Yak Intestinal Microbiota Using High-Throughput 16S rRNA Gene Sequencing
by Yanbin Zhu, Yangji Cidan, Munwar Ali, Sijia Lu, Usama Javed, Zhuoma Cisang, Deji Gusang, Quzha Danzeng, Kun Li and Wangdui Basang
Vet. Sci. 2025, 12(3), 208; https://doi.org/10.3390/vetsci12030208 - 1 Mar 2025
Cited by 1 | Viewed by 800
Abstract
This study investigated the impact of varying dietary protein–energy ratios on the intestinal microbiota composition in postpartum weaned female yak. For this study, forty yaks were divided into four groups and provided with different dietary treatments (group FA: high-energy high-protein, FB: high-energy low-protein, [...] Read more.
This study investigated the impact of varying dietary protein–energy ratios on the intestinal microbiota composition in postpartum weaned female yak. For this study, forty yaks were divided into four groups and provided with different dietary treatments (group FA: high-energy high-protein, FB: high-energy low-protein, FC: low-energy high-protein, and FD: control group, provided with 48% alfalfa hay, 48% oat grass, and 4% premix) to investigate the variations in microflora profiles and metabolic responses. Rectal fecal samples (n = 24 × 2) were collected at day 15 and 30, from all four groups, and total DNA was extracted to estimate microbial heterogeneity and community structures by 16S rRNA sequencing focusing V3–V4 regions, using the Illumina Nova Seq 6000 platform. The results revealed a total of 5,669,645 raw data sequences (3,189,115 and 2,480,530 from day 15 and day 30, respectively). Results showed that groups FA and FB had enhanced protein metabolism and microbial diversity, which was marked by a significant increase (p < 0.05) in abundance of Ruminococcus. Conversely, the FD group showed a low level of microbial diversity with a significant (p < 0.05) predominance of Clostridium and Proteobacteria, indicating microbial dysbiosis and metabolic stress. It was concluded that imbalanced diets (groups FC and FD) upregulated the stress-related pathways with no favorable microbial shifts, whereas, dietary treatments in group FA and FB significantly (p < 0.05) supported the pathways involved in amino acids and carbohydrate metabolism and beneficially shifted the gut microbiota. These findings emphasize the importance of postpartum supplementation with appropriate proportions of protein and energy feed to promote optimal microbial health and metabolic functioning, particularly for yaks inhabiting high-altitude regions, which is a challenging environment. Full article
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Review

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22 pages, 1133 KiB  
Review
Gut Barrier Dysfunction and Microbiota Variations in Cryptosporidiosis: A Comprehensive Review
by Munwar Ali, Chang Xu, Mingyue Wang, Qazal Hina, Yaru Ji, Subiha Anwar, Sijia Lu, Qing He, Yawei Qiu and Kun Li
Vet. Sci. 2025, 12(2), 85; https://doi.org/10.3390/vetsci12020085 - 23 Jan 2025
Viewed by 1364
Abstract
Cryptosporidiosis is a zoonotic protozoan parasite-born disease, equally significant in both animals and humans, especially affecting immunocompromised individuals (e.g., AIDS patients) and neonates. The prime concerns of this review article are to demonstrate the disruption of the intestinal barrier and variations in the [...] Read more.
Cryptosporidiosis is a zoonotic protozoan parasite-born disease, equally significant in both animals and humans, especially affecting immunocompromised individuals (e.g., AIDS patients) and neonates. The prime concerns of this review article are to demonstrate the disruption of the intestinal barrier and variations in the gut microbiome during cryptosporidiosis, and to explore host gut–parasite interactions that can lead to the development of novel therapeutics. The review concluded that the enteric barrier is particularly maintained by tight junction proteins (e.g., occludin, claudin, and ZO-1, etc.) and mucosal immunity, both of which are severely compromised during Cryptosporidium spp. infections, resulting in increased intestinal barrier permeability, inflammatory responses, diarrhea, and ultimately death in severe cases. Cryptosporidium-induced dysbiosis is characterized by reduced microbial diversity and richness, a shift from commensal to pathogenic bacteria, as evidenced by increased pro-inflammatory taxa like Proteobacteria, and reduced proportions of beneficial SCFAs producing bacteria, e.g., Firmicutes. Recent investigations have highlighted the interrelations between gut microbiota and epithelial barrier integrity, especially during cryptosporidiosis, demonstrating the modulations regarding tight junctions (TJs), immune reactions, and SCFA production, all of which are main players in alleviating this protozoal parasitic infection. This review comprehensively describes the fine details underlying these impairments, including autophagy-mediated TJs’ degradation, inflammasome activation, and gut microbiome-driven alterations in metabolic pathways, providing the latest relevant, and well-organized piece of knowledge regarding intestinal barrier alterations and microbial shifts during cryptosporidiosis. This work emphasizes the future need for longitudinal studies and advanced sequencing techniques to understand host gut microbiota–parasite interactions, aiming to formulate innovative strategies to mitigate cryptosporidiosis. Full article
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