The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.

The use of analgosedatives in critically ill patients carries the risk of impairing gastrointestinal (GI) propulsion and could thereby lead to sepsis. The gut microbiota can influence GI motility, but whether GI microbial dysbiosis modifies GI peristalsis impairment by analgosedative drugs has not yet been analysed. This question was addressed in the guinea pig small intestine following a decrease of bacterial load by antibiotic pretreatment.

Guinea pigs were enorally (within the mouth) pretreated with meropenem, neomycin and vancomycin, and antibiotic-induced decrease of bacterial load was confirmed by 16S rDNA sequencing. Peristalsis in the isolated guinea pig small intestine was evaluated by determining the pressure threshold at which a peristaltic wave is triggered. The expression of factors that may be relevant to communication between GI microbiota and the motor system was examined at the mRNA (quantitative (q)PCR]) and/or protein (enzyme-linked immunosorbent assay [ELISA]) level.

Antibiotic treatment disturbed the small intestinal microbiome as shown by decrease of bacterial load and reduced alpha diversity. Microbial dysbiosis did not affect peristalsis at baseline but blunted the ability of α2 agonists to inhibit peristalsis, while the anti-peristaltic effects of sufentanil, midazolam, neostigmine and propofol were inconsistently affected. These functional alterations were complemented by a decreased expression of α2-adrenoceptors, toll-like receptors (TRL) 3, 4 & 7, IFN-γ and iNOS.

Antibiotic-induced decrease of bacterial load in the small intestine selectively blunts the ability of α2 agonists to impair peristalsis. This effect is explained by decreased α2-adrenoceptor expression, which may arise from TLR down-regulation in the dysbiotic gut.

The intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.

Intestinal anastomosis is a critical procedure in both emergency and elective surgeries to maintain intestinal continuity. However, the incidence of anastomotic leakage (AL) has recently increased, reaching up to 20%, imposing major clinical and economic burdens. Substantial perioperative alterations in the intestinal microbiota composition may contribute to AL, particularly due to disruptions in key microbial populations essential for intestinal health and healing. The intricate interplay between the intestinal microbiota and the host immune system, along with microbial changes before and during surgery, significantly influences anastomotic integrity. Notably, specific pathogens such as Enterococcus and Pseudomonas aeruginosa have been implicated in AL pathogenesis. Preventive strategies including dietary regulation, personalized intestinal preparation, microbiota restoration and enhanced recovery after surgery protocols, may mitigate AL risks. Future research should focus on elucidating the precise mechanisms linking intestinal microbiota alterations to anastomotic healing and developing targeted interventions to improve surgical outcomes.

Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD. We investigated the phagocyte-associated microbiome using an unbiased sequencing approach to identify potential pathobionts and elucidate the host response to these microbes.

We collected ileal and colonic mucosal biopsies from CD patients and controls without inflammatory bowel disease (IBD), isolated lamina propria phagocytes (CD11b+ cells), and performed deep RNA sequencing (n = 37). Reads were mapped to the human genome for host gene expression analysis and a prokaryotic database for microbiome taxonomic and metatranscriptomic profiling. Results were confirmed in a second IBD cohort (n = 17). Lysed lamina propria cells were plated for bacterial culturing; isolated colonies underwent whole genome sequencing (n = 11).

Crohn's disease ileal phagocytes contained higher relative abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp. than those from controls. CD phagocyte-associated microbes had increased expression of lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with a higher pathobiont burden showed increased expression of pro-inflammatory and antimicrobial genes, including PI3 (antimicrobial peptide) and BPIFB1 (LPS-binding molecule). E. coli isolated from the CD lamina propria had more flagellar motility and antibiotic resistance genes than control-derived strains.

Lamina propria resident phagocytes harbor bacterial strains that may act as pathobionts in CD. Our findings shed light on the role of pathobionts and the immune response in CD pathogenesis and suggest new targets for therapies.

Ulcerative colitis (UC) is believed to be triggered by a dysregulated inflammatory response to the intestinal microbiota. Acyloxyacyl hydrolase (AOAH) is a unique host lipase that inactivates Gram-negative bacterial lipopolysaccharides (LPS). After finding that AOAH produced in the intestine decreases stimulatory LPS levels in colon contents, we used the dextran sodium sulfate (DSS) model to test the enzyme's ability to prevent colitis in mice. We found that AOAH played a protective role by decreasing colonic inflammation, tissue injury, and barrier permeability. Increasing or decreasing intestinal LPS abundance exacerbated or alleviated colitis, respectively, suggesting that AOAH prevents colitis by reducing stimulatory intestinal LPS levels. AOAH also mitigated colitis-associated colorectal cancer. This highly conserved enzyme may exert its protective effects by preventing LPS-induced injury to the epithelial cell mitochondria that are important for restoring the mucosal epithelial barrier after injury. By decreasing intestinal levels of stimulatory LPS, AOAH prevents colitis and colorectal cancer.

Persistent intestinal inflammation is a major contributor to various diseases, including digestive disorders, immune dysregulation, and cancer. The NF-κB signaling pathway is pivotal in the inflammatory response of intestinal cells, regulating the secretion of inflammatory factors, mediating signal transduction, and activating receptors. In colitis, NF-κB signaling and its effector molecules are excessively activated by various stimuli, leading to overexpression of inflammatory mediators and immune regulators. Colitis, an inflammation of the intestinal mucosa, underlies many intestinal diseases, with increasing incidence. Traditional treatments such as glucocorticoids and nonsteroidal antiinflammatory drugs have significant limitations and side effects. Pogostemon cablin, a traditional Chinese medicine and food, is widely used in food, spices, and pharmaceuticals. Studies have demonstrated its positive therapeutic effects on intestinal inflammation, primarily through regulation of the NF-κB signaling pathway. Moreover, P. cablin and its active components exhibit pharmacological activities such as antiapoptotic, antioxidant, and antitumor effects. This review summarizes the original research on treating intestinal mucosal inflammation via NF-κB signaling regulation using P. cablin and its active components, providing new insights for colitis treatment.

Inflammatory bowel disease (IBD) patients display genetic polymorphisms in toll-like receptor 4 (TLR4) genes, contributing to dysregulate enteric nervous system (ENS) circuits with increased levels of 5-HT and alteration of the neuroimmune crosstalk. In this study, we investigated the impact of TLR4 signalling on mouse ENS dysfunction caused by dextran sulphate sodium (DSS)-induced ileitis.

Male C57BL/6J (wild-type [WT]) and TLR4-/- mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and then were switched to 3-day regular drinking water. Histological analysis and proinflammatory cytokine mRNA levels were assessed in ileal samples. Gut motility was evaluated by changes in transit of a fluorescent-labelled marker and isometric neuromuscular responses of ileal full-thickness segments to receptor and non-receptor-mediated stimuli. Alterations in ENS architecture were assessed by confocal immunohistochemistry in longitudinal muscle-myenteric plexus whole-mount preparations.

In WT mice, DSS treatment caused delayed gastrointestinal transit, ileal myenteric neurodegeneration, reactive gliosis and release of proinflammatory cytokines. Enhanced cholinergic and tachykinergic excitatory tone, increased inducible nitric oxide synthase (iNOS)-mediated relaxation, and changes in 5-HT2A and 5-HT3 receptor-mediated responses were observed during ileitis in WT mice. TLR4 deficiency reversed most of the functional and morphological abnormalities.

Our results demonstrate that TLR4 activity influences the severity of ileitis, neuroglial plasticity, gut motility, and nitrergic and 5-HTergic neurotransmissions. The neuroimmune interaction between TLR4 and 5-HT observed in our study appears to be a potential pharmacological target to treat ENS dysfunction implicated in IBD onset/progression.

Alterations in goblet cell biology constitute one of the most effective host responses against enteric parasites. In the gastrointestinal (GI) tract, millions of bacteria influence these goblet cell responses by binding to pattern recognition receptors such as toll-like receptors (TLRs). Studies suggest that the gut microbiota also interacts bidirectionally with enteric parasites, including Trichuris muris. Here, we study the roles of T. muris-altered microbiota and the TLR2-SPDEF axis in parasitic host defense. In acute T. muris infection, we observed altered gut microbiota composition, which, when transferred to germ-free mice, resulted in increased goblet cell numbers, Th2 cytokines and Muc2 expression, as well as increased Tlr2. Further, antibiotic (ABX)-treated TLR2-/- mice, despite having received the same T. muris-altered microbiota, displayed diminished Th2 response, Muc2 expression, and, intriguingly, diminished SPDEF expression compared to wildtype counterparts. When infected with T. muris, SPDEF-/- mice exhibited a reduced Th2 response and altered microbial composition compared to SPDEF+/+, particularly on day 14 post-infection, and this microbiota was sufficient to alter host goblet cell response when transferred to ABX-treated mice. Taken together, our findings suggest the TLR2-SPDEF axis, via T. muris-induced microbial changes, is an important regulator of goblet cell function and host's parasitic defense.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously affects the life expectancy of patients. Although increasingly sophisticated combinations of drugs can alleviate symptoms, 10-20% of patients still do not respond well. Therefore, it is necessary to further explore the pathogenesis and potential biomarkers of UC. Many clues have suggested the important value of mitochondrial metabolism in UC, but its role and related targets need to be further explored. By public database data, we identified differentially expressed mitochondrial metabolism related genes (MMRG) in UC. Subsequently, we identified biomarkers associated with MMRG based on a machine learning approach. After classifying the MMRG-associated molecular subtypes of UC, we comprehensively analyzed the MMRG biomarkers and the relationship between the MMRG molecular subtypes and immune infiltration characteristics. Single-cell sequencing analysis showed significant expression pattern of MMRG signatures in different cell subtypes. qRT-PCR and western blot further confirmed the abnormal expressions of selected genes in vitro. Our findings provided a new perspective on the role of MMRG in UC.

Biomimetic gut models show promise for enhancing our understanding of intestinal disorder pathogenesis and accelerating therapeutic strategy development. Currentin vitromodels predominantly comprise traditional static cell culture and animal models. Static cell culture lacks the precise control of the complex microenvironment governing human intestinal function. Animal models provide greater microenvironment complexity but fail to accurately replicate human physiological conditions due to interspecies differences. As the available models do not accurately reflect the microphysiological environment and functions of the human intestine, their applications are limited. An optimal approach to intestinal modeling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. This review highlights biofabrication strategies for constructing biomimetic intestinal models and research approaches for simulating key intestinal physiological features. We also discuss potential biomedical applications of these models and provide an outlook on multi-scale intestinal modeling.

Recently, the "epithelial barrier hypothesis" has been proposed as a key factor in the development of allergic diseases, such as food allergies. Harmful environmental factors can damage epithelial barriers, with detrimental effects on the host immune response and on the local microbial equilibrium, resulting in chronic mucosal inflammation that perpetuates the dysfunction of the epithelial barrier. The increased epithelial permeability allows allergens to access the submucosae, leading to an imbalance between type 1 T-helper (Th1) and type 2 T-helper (Th2) inflammation, with a predominant Th2 response that is the key factor in food allergy development. In this article on the state of the art, we review scientific evidence on the "epithelial barrier hypothesis", with a focus on food allergies. We describe how loss of integrity of the skin and intestinal epithelial barrier and modifications in gut microbiota composition can contribute to local inflammatory changes and immunological unbalance that can lead to the development of food allergies.

Maternal high fat diet (MHFD) increased colitis susceptibility in adulthood. However, the mechanism remains unclear. We sought to explore whether novel gut immune receptor leucine-rich repeat C19 (LRRC19) contributed to the impaired mucus barrier of offspring exposed to MHFD via gut immune response and microbiota. The results showed that MHFD significantly impaired the intestinal mucus barrier of offspring, and up-regulated the expression of LRRC19. Lrrc19 deletion alleviated the mucus barrier disruption. Mechanistically, metagenome sequencing revealed that the MHFD-induced gut microbiota alteration was partly restored in Lrrc19-/- offspring. Muc2-associated bacteria were decreased in the MHFD group, such as Akkermansia_muciniphila_CAG_154, which increased in the Lrrc19-deficient offspring. Moreover, Lrrc19-/- offspring had a higher rate of indole-3-acetic acid (IAA)-producing bacterium, such as Lactobacillus reuteri. A targeted metabolomics analysis revealed that IAA emerged as the top candidate that might mediate the protective effects. IAA was found to improve the mucus barrier function by increasing the ratio of interleukin-22 (IL-22)+ ILC3 cells in an aryl hydrocarbon receptor (AhR)-dependent manner. These results suggest that MHFD disrupts the intestinal mucus barrier of offspring through regulating gut immune receptor LRRC19 and inducing an imbalance of gut microbiota and microbiota-derived metabolites.

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of gastrointestinal dysfunction drive and then perpetuate multi-organ dysfunction syndrome. Despite the clear importance of maintaining gut homeostasis, there are very few reliable measures of gut function in critical illness. Further, while multiple therapeutic strategies have been proposed, most have not been shown to conclusively demonstrate benefit, and care is still largely supportive. The key role of the gut in critical illness was the subject of the tenth Perioperative Quality Initiative meeting, a conference to summarize the current state of the literature and identify key knowledge gaps for future study. This review is the product of that conference.

Host-microbiome-dietary interactions play crucial roles in regulating human health, yet their direct functional assessment remains challenging. We adopted metagenome-informed metaproteomics (MIM), in mice and humans, to non-invasively explore species-level microbiome-host interactions during commensal and pathogen colonization, nutritional modification, and antibiotic-induced perturbation. Simultaneously, fecal MIM accurately characterized the nutritional exposure landscape in multiple clinical and dietary contexts. Implementation of MIM in murine auto-inflammation and in human inflammatory bowel disease (IBD) characterized a "compositional dysbiosis" and a concomitant species-specific "functional dysbiosis" driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutritional MIM assessment enabled the determination of IBD-related consumption patterns, dietary treatment compliance, and small intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.

Inflammatory bowel disease (IBD) is a chronic or recurrent inflammatory disorder affecting various parts of the gastrointestinal tract. Metformin, a widely prescribed hypoglycemic drug for type 2 diabetes, has shown potential in reducing IBD risk. However, its oral administration faces significant challenges due to the harsh gastrointestinal environment, requiring higher or more frequent doses to achieve therapeutic effects, which increases the risk of side effects. To address this, we developed alginate-shelled hydrogel microcapsules with a thin oil layer for targeted intestinal delivery of metformin. The oil layer protects metformin from gastric acid and ensures its release specifically in the intestines. In a dextran sulfate sodium-induced colitis mouse model, metformin-loaded hydrogel microcapsules (MHM) significantly reduced disease activity, intestinal epithelial damage, and macrophage infiltration linked to pro-inflammatory cytokine factors. Additionally, MHM improved dysbiosis of specific bacterial genera, including Bacteroides vulgatus, Lactobacillus (L.) gasseri, L. reuteri, and L. intestinalis, optimizing the abundance and composition of microorganisms. These findings indicate that encapsulating metformin within alginate shelled-microcapsules with a thin oil layer presents a potential delivery system for IBD treatment.

The intestinal area is composed of diverse cell types that harmonize gut homeostasis, which is influenced by both endogenous and exogenous factors. Notably, the environment of the intestine is exposed to several types of mechanical forces, including shear stress generated by fluid flow, compression and stretch generated by luminal contents and peristaltic waves of the intestine, and stiffness attributed to the extracellular matrix. These forces play critical roles in the regulation of cell proliferation, differentiation, and migration. Many efforts have been made to simulate the actual intestinal environment in vitro. The three-dimensional organoid culture system has emerged as a powerful tool for studying the mechanism of the intestinal epithelial barrier, mimicking rapidly renewing epithelium from intestinal stem cells (ISCs) in vivo. However, many aspects of how mechanical forces, such as shear stress, stiffness, compression, and stretch forces, influence the intestinal area remain unresolved. Here, we review the recent studies elucidating the impact of mechanical forces on intestinal immunity, interaction with the gut microbiome, and intestinal diseases.

Pogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified.

To elucidate the pharmacological mechanisms of PEO for treating UC.

In the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO's anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated.

This study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.

Bats are considered natural hosts for numerous viruses. Their ability to carry viruses that cause severe diseases or even death in other mammals without falling ill themselves has attracted widespread research attention. Toll-like receptor 2 forms heterodimers with Toll-like receptor 1 or Toll-like receptor 6 on cell membranes, recognizing specific pathogen-associated molecular patterns and playing a key role in innate immune responses. Previous studies have shown that moderate Toll-like receptor 2-mediated immune signals aid in pathogen clearance, while excessive or inappropriate Toll-like receptor 2-mediated immune signals can cause self-damage. In this study, we observed that TLR2, unlike TLR1 or TLR6, has undergone relaxed selection in bats compared with other mammals, indicating a reduced functional constraint on TLR2 specifically in bats. Indeed, our cell-based functional assays demonstrated that the ability of Toll-like receptor 2 to bind with Toll-like receptor 1 or Toll-like receptor 6 was significantly reduced in bats, leading to dampened inflammatory signaling. We identified mutations unique to bats that were responsible for this observation. Additionally, we found that mutations at residues 375 and 376 of Toll-like receptor 2 in the common ancestor of bats also resulted in reduced inflammatory response, suggesting that this reduction occurred early in bat evolution. Together, our study reveals that the Toll-like receptor 2-mediated inflammatory response has been specifically dampened in bats, which may be one of the reasons why they could harbor many viruses without falling ill.

Gut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination.

The review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized.

Literature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation.

The review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases.

Being absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

This study aims to investigate the effects of levan on the progression of hyperuricemia (HUA) rats and elucidate its underlying mechanisms. After levan intervention, both low and high-dose groups exhibited a significant decrease in serum uric acid (UA) levels, reaching 71.0 % and 77.5 %, respectively, compared to the model group. Furthermore, levan could alleviate renal pathological damage caused by glomerular cell vacuolation, inflammatory infiltration and collagen deposition. The results of enzyme activity assay and real-time fluorescence quantitative PCR showed that levan decreased UA production by inhibiting adenosine deaminase (ADA) activity and gene expression in liver; it upregulated ATP-binding cassette subfamily G member 2 protein (ABCG2) and organic anion transporter 1 (OAT1) transporter gene expression in the kidney, promoting UA excretion. Gut microbiome analysis indicated that levan regulated gut flora dysbiosis induced by HUA, resulting in up-regulated the abundance of beneficial bacteria (Muribaculaceae, Faecalibaculum, Bifidobacterium, and Lactobacillus) and decreased conditioned pathogenic bacteria (Escherichia_Shigella and Proteus). Non-targeted metabolomics showed changes in various serum metabolites associated with glycerophospholipid metabolism, lipid metabolism, and inflammation following oral administration of levan. Therefore, levan may be a promising functional dietary supplement for regulating the gut flora and remodeling of metabolic disorders in individuals with HUA.

Ulcerative colitis is a chronic relapsing-remitting and potentially progressive form of inflammatory bowel disease in which there is extensive inflammation and mucosal damage in the colon and rectum as a result of an abnormal immune response. MV130 is a mucosal-trained immunity-based vaccine used to prevent respiratory tract infections in various clinical settings. Additionally, MV130 may induce innate immune cells that acquire anti-inflammatory properties and promote tolerance, which could have important implications for chronic inflammatory diseases such as ulcerative colitis. This work demonstrated that the prophylactic administration of MV130 substantially mitigated colitis in a mouse model of acute colitis induced by dextran sulphate sodium. MV130 downregulated systemic and local inflammatory responses, maintained the integrity of the intestinal barrier by preserving the enterocyte layer and goblet cells, and reduced the oedema and fibrosis characteristic of the disease. Mechanistically, MV130 significantly reduced the infiltration of neutrophils and pro-inflammatory macrophages in the intestinal wall of the diseased animals and favoured the appearance of M2-polarised macrophages. These results suggest that MV130 might have therapeutic potential for the treatment of ulcerative colitis, reducing the risk of relapse and the progression of disease.

Enteric virus infection is a major public health issue worldwide. Enteric viruses have become epidemic infectious diseases in several countries. Enteric viruses primarily infect the gastrointestinal tract and complete their life cycle in intestinal epithelial cells. These viruses are transmitted via the fecal-oral route through contaminated food, water, or person to person and cause similar common symptoms, including vomiting, abdominal pain, and diarrhea. Diarrheal disease is the third leading cause of death in children under five years of age, accounting for approximately 1.7 billion cases and 443,832 deaths annually in this age group. Additionally, some enteric viruses can invade other tissues, leading to severe conditions and even death. The pathogenic mechanisms of enteric viruses are also unclear. In this review, we organized the research on trending enteric virus infections, including rotavirus, norovirus, adenovirus, Enterovirus-A71, Coxsackievirus A6, and Echovirus 11. Furthermore, we discuss the gastrointestinal effects and pathogenic mechanisms of SARS-CoV-2 in intestinal epithelial cells, given the gastrointestinal symptoms observed during the COVID-19 pandemic. We conducted a literature review on their pathogenic mechanisms, which serves as a guide for formulating future treatment strategies for enteric virus infections.

The current study investigated the effects of mulberry 1-deoxynijirimycin (DNJ) on the digestion ability, intestinal morphology, and intestinal barrier of rabbits.

A total of 36 New Zealand White rabbits (male) about 45 days old (mean body weight of 1.05±0.04 kg) were reared and commercial diets were employed, and afterwards divided into three groups (n = 12) with different levels of DNJ extract additive in feed: T0 (0 g/kg), T1 (0.35 g/kg), T2 (0.7 g/kg) for 28 d.

The results demonstrated that T2 decreased the average daily gain (p<0.05). T1 and T2 decreased villus height and inflammatory factor levels as compared with T0 (p<0.05). DNJ significantly decreased the content of valeric acid (p<0.05). The content of acetic acid, propionic acid, iso butyric acid, iso valeric acid in T1 were higher than those in T0 and T2 (p<0.05). The content of butyric acid in T2 was lower than it in T0 and T1 (p<0.05). The content of caproic acid was firstly improved then reduced as the DNJ concentration improved (p<0.05). T2 significantly increased the abundance of dgA-11_gut_group and Christensenellaceae_R-7_group while decreased Bacteroide and Ralstonia as compared with T0 (p<0.05). Compared with T0, T1, and T2 significantly improved the gene expression of JAM2, JAM3, mucin4, mucin6 (p<0.05), T1 significantly decreased the expression of occluding while T2 significantly increased (p<0.05), T2 significantly increased the expression of claudin1 and claudin2 (p<0.05).

DNJ at high level changed microbiome compositions, inhibited inflammation, and improved intestinal barrier while it decreased the growth performance and shorted villus height in rabbit jejunum by regulating short chain fatty acid compositions in rabbits.

The four members of the p90 ribosomal S6 kinase (RSK) family are serine/threonine protein kinases, which are phosphorylated and activated by ERK1/2. RSK1/2/3 are further phosphorylated by PDK1. Receiving inputs from two major signaling pathways places RSK as a key signaling node in numerous pathologies. A plethora of RSK1/2 substrates have been identified, and in the majority of cases the causative roles these RSK substrates play in the pathology are unknown.

The majority of studies have focused on RSK1/2 and their functions in a diverse group of cancers. However, RSK1/2 are known to have important functions in cardiovascular disease and neurobiological disorders. Based on the literature, we identified substrates that are common in these pathologies with the goal of identifying fundamental physiological responses to RSK1/2.

The core group of targets in pathologies driven by RSK1/2 are associated with the immune response. However, there is a paucity of the literature addressing RSK function in inflammation, which is critical to know as the pan RSK inhibitor, PMD-026, is entering phase II clinical trials for metastatic breast cancer. A RSK inhibitor has the potential to be used in numerous diverse diseases and disorders.

Growing evidence has proved that alterations in the gut microbiota have been linked to neurological disorders including stroke. Structural and functional disruption of the blood-brain barrier (BBB) is observed after stroke. In this context, there is pioneering evidence supporting that gut microbiota may be involved in the pathogenesis of stroke by regulating the BBB function. However, only a few experimental studies have been performed on stroke models to observe the BBB by altering the structure of gut microbiota, which warrant further exploration. Therefore, in order to provide a novel mechanism for stroke and highlight new insights into BBB modification as a stroke intervention, this review summarizes existing evidence of the relationship between gut microbiota and BBB integrity and discusses the mechanisms of gut microbiota on BBB dysfunction and its role in stroke.

Curcumin is a natural food ingredient and has the potential to alleviate inflammation and combat cancer. The incidence of intestinal inflammation has been increasing and poses a severe risk to human health. Due to low absorption and bioavailability, curcumin's anti-inflammatory ability is ineffective. To improve the bioavailability of curcumin, descriptions of the intestinal barrier, signaling pathways, and transport mechanisms are reviewed. Blocking the signaling pathways lowers the number of inflammatory cytokines produced, which is the primary mechanism by which curcumin relieves inflammatory symptoms. The bioavailability of curcumin is not only related to physicochemical properties but also to the nature of the carrier material. Environmental indicators also have an impact on the improvement of curcumin bioavailability in applications. There is a need to develop multifunctional and more stable nanomaterial targeting systems to improve curcumin bioavailability and achieve better results in nanotechnology research and targeted inflammation therapy.

Radiation colitis is one of the most common complications in patients undergoing pelvic radiotherapy and there is no effective treatment in the clinic. Therefore, searching for effective agents for the treatment of radiation colitis is urgently needed. Herein, it is found that the essential element selenium (Se) is protective against radiation colitis through inhibiting X-ray-induced apoptosis, cell cycle arrest, and inflammation with the involvement of balancing the generation of reactive oxygen species after the irradiation. Mechanistically, Se, especially for selenium nanoparticles (SeNPs), induced selenoprotein expression and then functioned to effectively restrain DNA damage response, which reduced X-ray-induced intestinal injury. Additionally, SeNPs treatment also restrained the cyclic GMP-AMP synthas (cGAS)- stimulator of interferon genes (STING)-TBK1-IRF3 signaling pathway cascade, thereby blocking the transcription of inflammatory cytokine gene, IL-6 and TNF-α, and thus alleviating inflammation. Moreover, inducing selenoprotein expression, such as GPX4, with SeNPs in vivo can regulate intestinal microenvironment immunity and gut microbiota to attenuate radiation-induced colitis by inhibiting oxidative stress and maintaining microenvironment immunity homeostasis. Together, these results unravel a previously unidentified modulation role that SeNPs restrained radiation colitis with the involvement of inducing selenoprotein expression but suppressing cGAS-STING-TBK1-IRF3 cascade.

Dihydromyricetin (DMY), a natural flavonoid compound, are believed to prevent inflammatory response, dealing with pathogens and repairing the intestinal barrier. The objective of this study was to investigate whether DMY supplementation could attenuate intestinal damage in the context of enterotoxigenic Escherichia coli K88 (ETEC F4+) infection. After weaning, different litters of pigs were randomly assigned to one of the following treatments: (1) non-challenged control (CON, fed with basal diet); (2) ETEC-challenged control (ECON, fed with basal diet); and (3) ETEC challenge + DMY treatment (EDMY, fed with basal diet plus 300 mg kg-1 DMY). We observed a significant reduction in fecal Escherichia coli shedding and diarrhea incidence, but an increase in ADG in pigs of EDMY group compared to the pigs of ECON group. Relative to the pigs of ECON group, dietary DMY treatment decreased (P < 0.05) concentrations of the serum D-xylose, D-lactate and diamine oxidase (DAO), but increased the abundance of zonula occludens-1 (ZO-1) in the jejunum of pigs. In addition, DMY also decreased (P < 0.05) the number of S-phase cells and the percentage of total apoptotic epithelial cells of jejunal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Furthermore, DMY decreased the mRNA expression levels of critical immune-associated genes TLR4, NFκB, Caspase3, Caspase9, IL-1β, IL-6, TNF-α and the protein p-NFκB and p-IκBα expressions of intestinal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Compared to the ECON group, DMY elevated (P < 0.05) the expression levels of β-defensins PBD1, PBD2, PBD3, PBD129, as well as the abundance of secreted IgA in intestinal mucosae of the EDMY group. Thus, our results indicate that DMY may relieve intestinal integrity damage due to Escherichia coli F4.

The emerging function of short-chain fatty acids (SCFAs) in Parkinson's disease (PD) has been investigated in this article. SCFAs, which are generated via the fermentation of dietary fiber by gut microbiota, have been associated with dysfunction of the gut-brain axis and, neuroinflammation. These processes are integral to the development of PD. This article examines the potential therapeutic implications of SCFAs in the management of PD, encompassing their capacity to modulate gastrointestinal permeability, neuroinflammation, and neuronal survival, by conducting an extensive literature review. As a whole, this article emphasizes the potential therapeutic utility of SCFAs as targets for the management and treatment of PD.

Microbes play a significant role in human tumor development and profoundly impact treatment efficacy, particularly in immunotherapy. The respiratory tract extensively interacts with the external environment and possesses a mucosal immune system. This prompts consideration of the relationship between respiratory microbiota and lung cancer. Advancements in culture-independent techniques have revealed unique communities within the lower respiratory tract. Here, we provide an overview of the respiratory microbiota composition, dysbiosis characteristics in lung cancer patients, and microbiota profiles within lung cancer. We delve into how the lung microbiota contributes to lung cancer onset and progression through direct functions, sustained immune activation, and immunosuppressive mechanisms. Furthermore, we emphasize the clinical utility of respiratory microbiota in prognosis and treatment optimization for lung cancer.

Inflammatory bowel disease (IBD) is a persistent inflammatory illness of the gastrointestinal tract (GIT) triggered by an inappropriate immune response to environmental stimuli in genetically predisposed persons. Unfortunately, IBD patients' quality of life is negatively impacted by the symptoms associated with the disease. The exact etiology of IBD pathogenesis is not fully understood, but the emerging research indicated that the microRNA (miRNA) plays an important role. miRNAs have been documented to possess a significant role in regulating pro- and anti-inflammatory pathways, in addition to their roles in several physiological processes, including cell growth, proliferation, and apoptosis. Variations in the miRNA profiles might be a helpful prognostic indicator and a valuable tool in the differential diagnosis of IBD. Most interestingly, these miRNAs have a promising therapeutic target in several pre-clinical animal studies and phase 2 clinical studies to alleviate inflammation and improve patient's quality of life. This comprehensive review discusses the current knowledge about the significant physiological role of different miRNAs in the health of the intestinal immune system and addresses the role of the most relevant differentially expressed miRNAs in IBD, identify their potential targets, and emphasize their diagnostic and therapeutic potential for future research.

Intestinal stem cells (ISCs) play a crucial role in maintaining the equilibrium and regenerative potential of intestinal tissue, thereby ensuring tissue homeostasis and promoting effective tissue regeneration following injury. It has been proven that targeting Toll-like receptors (TLRs) can help prevent radiation-induced damage to the intestine. In this study, we established an intestinal injury model using IR and evaluated the effects of CL429 on ISC regeneration both in vivo and in vitro. Following radiation exposure, mice treated with CL429 showed a significant increase in survival rates (100% survival in the treated group compared to 54.54% in the control group). CL429 also showed remarkable efficacy in inhibiting radiation-induced intestinal damage and promoting ISC proliferation and regeneration. In addition, CL429 protected intestinal organoids against IR-induced injury. Mechanistically, RNA sequencing and Western blot analysis revealed the activation of the Wnt and Hippo signaling pathways by CL429. Specifically, we observed a significant upregulation of YAP1, a key transcription factor in the Hippo pathway, upon CL429 stimulation. Furthermore, knockdown of YAP1 significantly attenuated the radioprotective effect of CL429 on intestinal organoids, indicating that CL429-mediated intestinal radioprotection is dependent on YAP1. In addition, we investigated the relationship between TLR2 and YAP1 using TLR2 knockout mice, and our results showed that TLR2 knockout abolished the activation of CL429 on YAP1. Taken together, our study provides evidence supporting the role of CL429 in promoting ISC regeneration through activation of TLR2-YAP1. And further investigation of the interaction between TLRs and other signaling pathways may enhance our understanding of ISC regeneration after injury.