Starvation stress is one of the most common environmental challenges faced by aquatic animals, often leading to compensatory growth, a widespread phenomenon in the animal kingdom, especially among aquatic species. The sea cucumber (Apostichopus japonicus), a key marine economic species in China, has been shown to utilize long non-coding RNAs (lncRNAs) in responding to environmental changes, pathogen infections, and tissue regeneration. In this study, strand-specific high-throughput sequencing was employed to analyze transcriptomic data from degenerated intestines of A. japonicus under starvation conditions. High-quality lncRNAs were identified and classified, and key differentially expressed mRNAs and lncRNAs associated with intestinal degradation were screened. A gene interaction network model based on the competing endogenous RNA (ceRNA) theory was then constructed. The analysis revealed that the "AjSOX9/Aja-miR-2012-5p/MSTRG.2956.1 and MSTRG.5699.1" axes, as well as the "AjWNT9B/Aja-miR-200-3p/MSTRG.19757.1 and MSTRG.21788.1" axes, play significant roles in degraded intestines and may promote intestinal regeneration during compensatory growth. Additionally, the "AjFABP2/Aja-miR-9-5p/MSTRG.9667.1" axis appears to regulate energy metabolism under starvation stress. These findings provide valuable insights into the non-coding gene regulatory networks in invertebrates under starvation stress and offer a scientific foundation for developing stress-resistant sea cucumber strains, contributing to the sustainable development of the sea cucumber aquaculture industry.

Prostaglandin E2 receptor type 4 (EP4) agonists have been shown to be effective in treating experimental ulcerative colitis (UC) in animals and in human clinical trials, but their development has been impeded by unacceptable systemic side effects. In this study, a series of methylene phosphate prodrugs of a highly potent and selective prostaglandin EP4 receptor agonist were designed to target and remain localized in the gastrointestinal (GI) tract after either oral or rectal instillation. The prodrugs were designed to be converted to liberate active EP4 agonist by intestinal alkaline phosphate (IAP), a ubiquitous enzyme found at the luminal of the intestinal wall thus exposing the colon epithelial barrier while reducing systemic exposure to the active agonist. The prodrugs were shown to hydrolyze in plasma and after contact with GI tissue slices from ileum and colon. When optimized prodrugs were dosed orally, systemic peak exposure to the active agonist was not reduced, presumably due to IAP activity in the duodenum and small intestine. However, when dosed rectally, the prodrugs gave much reduced levels of EP4 agonist in the blood. An optimized prodrug was shown to be retained in the colon, when compared with free agonist after rectal administration in healthy mice and to be efficacious in a model of UC (the DSS mouse model). Plasma exposure to the active agonist was also much reduced in the mouse model of UC after 4 days of rectal dosing but after 7 days, one DSS mouse showed elevated systemic levels of the free agonist in the blood. The concept of efficacy and intestinal retention of an EP4 agonist-methylene phosphate prodrug was proven for rectal instillation but in DSS treated mice, severe disease appears to compromise the epithelia barrier sufficiently to allow some absorption of the prodrug to occur. Thus, further optimization of these prodrugs is required before a candidate can be selected for development for treating severe ulcerative colitis.

Research has highlighted numerous detrimental consequences of thiamine deficiency on digestive function. These range from impaired gastric and intestinal motility to aberrant changes in pancreatic exocrine function, gastric acidity and disturbances in gut barrier integrity and inflammation. Thiamine and its pharmacological forms, as a primary or adjunctive therapy, have been shown to improve symptoms such as nausea, constipation, dysphagia and intestinal dysmotility, in both humans and animals. This review aims to explore molecular mechanisms underlying the therapeutic action of thiamine in gastrointestinal dysfunction. Our analysis demonstrates that thiamine insufficiency restricted to the gastrointestinal system, i.e., lacking well-known symptoms of dry and wet beriberi, may arise through (i) a disbalance between the nutrient influx and efflux in the gastrointestinal system due to increased demands of thiamine by the organism; (ii) direct exposure of the gastrointestinal system to oral drugs and gut microbiome, targeting thiamine-dependent metabolism in the gastrointestinal system in the first line; (iii) the involvement of thiamine in acetylcholine (ACh) signaling and cholinergic activity in the enteric nervous system and non-neuronal cells of the gut and pancreas, employing both the coenzyme and non-coenzyme actions of thiamine. The coenzyme action relies on the requirement of the thiamine coenzyme form - thiamine diphosphate - for the production of energy and acetylcholine (ACh). The non-coenzyme action involves participation of thiamine and/or derivatives, including thiamine triphosphate, in the regulation of ACh synaptic function, consistent with the early data on thiamine as a co-mediator of ACh in neuromuscular synapses, and in allosteric action on metabolic enzymes. By examining the available evidence with a focus on the gastrointestinal system, we deepen the understanding of thiamine's contribution to overall gastrointestinal health, highlighting important implications of thiamine-dependent mechanisms in functional gastrointestinal disorders.

Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions.

This study investigated the optimal tannic acid dosage and assessed tolerance levels in broiler chickens. In experiment 1, 525 broilers were randomly divided into 5 treatment groups, the control group (CON group) and groups TA1 to TA4, corresponding to treatments of 0.025, 0.05, 0.075, and 0.1 % tannic acid, respectively, to determine the effect of tannic acid on broiler growth performance and gut health. Experiment 2 was performed to evaluate the tolerance of tannic acid; 416 broilers were randomly divided into control (CTR), 0.075 % tannic acid (TA), 0.375 % tannic acid (5TA), and 0.75 % tannic acid (10TA) groups. In the first experiment, compared with that in the CON group, the growth performance and the ileal intestinal villi height to crypt depth ratio showed a quadratic curve increase with tannic acid supplementation (P < 0.05). Adding 0.05 % to 0.075 % tannic acid significantly improved the growth performance, intestinal morphology, and intestinal barrier function (P < 0.05). Tannic acid concentrations of 0.075 % significantly increased the abundance of Firmicutes and Lactobacillaceae in the ileum and decreased the abundance of Vibrionaceae and Yersiniaceae (P < 0.05). In experiment 2, the growth performance of the TA group significantly improved compared with that of the CTR group (P < 0.05). The F/G was significantly higher in the 5TA and 10TA groups than in the CTR group (P < 0.05), and the 10TA group had significantly reduced body weight on d 21 (P < 0.05). The addition of tannic acid resulted in significant glomerular and glandular hyperplasia, as well as muscularis thickening of the gizzard mucosa. However, broilers could not tolerate tannic acid doses of 0.375 % and above. Tannic acid supplementation may protect the proventriculus mucosal layer, reduce villi atrophy, and enhance growth performance by positively influencing the intestinal microbiota, villus morphology, and intestinal barrier function.

Background/Objectives:Campylobacter jejuni (CJ) is the etiological agent of the world's most common intestinal infectious food-borne disease, ranging from mild symptoms to fatal outcomes. The development of innovative synbiotics that inhibit the adhesion and reproduction of multidrug-resistant (MDR) CJ in animals and humans, thereby preserving intestinal homeostasis, is relevant. We have created a synbiotic based on the consortium of Lactobacillus crispatus 2029 (LC2029), Ligilactobacillus salivarius 7247 (LS7247), and a mannan-rich prebiotic (Actigen®). The purpose of this work was to study the in vitro anti-adhesive and antagonistic activities of the created synbiotic against MDR CJ strains, along with its role in preventing intestinal barrier dysfunction, which disrupts intestinal homeostasis. Methods: A complex of microbiological, immunological, and molecular biological methods was used. The ability of the LC2029 and LS7247 consortium to promote intestinal homeostasis in vitro was assessed by the effectiveness of controlling CJ-induced TLR4 activation, secretion of pro-inflammatory cytokines, development of intestinal barrier dysfunction, and production of intestinal alkaline phosphatase (IAP). Results: All MDR CJ strains showed marked adhesion to human Caco-2, pig IPEC-J2, chicken CPCE, and bovine BPCE enterocytes. For the first time, we found that the prebiotic and cell-free culture supernatant (CFS) from the consortium of LC2029 and LS7247 strains exhibit an additive effect in inhibiting the adhesion of MDR strains of CJ to human and animal enterocytes. CFS from the LC2029 and LS7247 consortium increased the permeability of the outer and inner membranes of CJ cells, which led to extracellular leakage of ATP and provided access to the peptidoglycan of the pathogen for the peptidoglycan-degrading bacteriocins nisin and enterolysin A produced by LS7247. The LC2029 and LS7247 consortium showed a bactericidal effect on CJ strains. Co-cultivation of the consortium with CJ strains resulted in a decrease in the viability of the pathogen by 6 log. CFS from the LC2029 and LS7247 consortium prevented the growth of CJ-induced TLR4 mRNA expression in enterocytes. The LC2029 and LS7247 consortium inhibited a CJ-induced increase in IL-8 and TNF-α production in enterocytes, prevented CJ-induced intestinal barrier dysfunction, maintained the transepithelial electrical resistance of the enterocyte monolayers, and prevented an increase in intestinal paracellular permeability and zonulin secretion. CFS from the consortium stimulated IAP mRNA expression in enterocytes. The LC2029 and LS7247 consortium and the prebiotic Actigen represent a new synergistic synbiotic with anti-CJ properties that prevents intestinal barrier dysfunction and preserves intestinal homeostasis. Conclusions: These data highlight the potential of using a synergistic synbiotic as a preventive strategy for creating feed additives and functional nutrition products based on it to combat the prevalence of campylobacteriosis caused by MDR strains in animals and humans.

Background/Objectives: The global emergence of antibiotic-resistant zooanthroponotic Escherichia coli strains, producing extended-spectrum beta-lactamases (ESBL-E) and persisting in the intestines of farm animals, has now led to the development of a pandemic of extra-intestinal infectious diseases in humans. The search for innovative probiotic microorganisms that eliminate ESBL-E from the intestines of humans and animals is relevant. Previously, we received three isolates of bifidobacteria: from milk of a calved cow (BLLT1), feces of a newborn calf (BLLT2) and feces of a three-year-old child who received fresh milk from this calved cow (BLLT3). Our goal was to evaluate the genetic identity of BLLT1, BLLT2, BLLT3 isolates using genomic DNA fingerprinting (GDF), to study the tolerance, adhesion, homeostatic and antibacterial activity of BLLT1 against ESBL-E. Methods: We used a complex of microbiological, molecular biological, and immunological methods, including next generation sequencing (NGS). Results: GDF showed that DNA fragments of BLLT2 and BLLT3 isolates were identical in number and size to DNA fragments of BLLT1. These data show for the first time the possibility of natural horizontal transmission of BLLT1 through with the milk of a calved cow into the intestines of a calf and the intestines of a child. BLLT1 was resistant to gastric and intestinal stresses and exhibited high adhesive activity to calf, pig, chicken, and human enterocytes. This indicates the unique ability of BLLT1 to inhabit the intestines of animals and humans. We are the first to show that BLLT1 has antibacterial activity against ESBL-E strains that persist in humans and animals. BLLT1 produced 145 ± 8 mM of acetic acid, which reduced the pH of the nutrient medium from 6.8 to 5.2. This had an antibacterial effect on ESBL-E. The genome of BLLT1 contains ABC-type carbohydrate transporter gene clusters responsible for the synthesis of acetic acid with its antibacterial activity against ESBL-E. BLLT1 inhibited TLR4 mRNA expression induced by ESBL-E in HT-29 enterocytes, and protected the enterocyte monolayers used in this study as a bio-model of the intestinal barrier. BLLT1 increased intestinal alkaline phosphatase (IAP) as one of the main molecular factors providing intestinal homeostasis. Conclusions: BLLT1 shows promise for the creation of innovative functional nutritional products for humans and feed additives for farm animals that will reduce the spread of ESBL-E strains in the food chain.

Familial dysautonomia (FD) is a rare sensory and autonomic neuropathy that results from a mutation in the ELP1 gene. Virtually all patients report gastrointestinal (GI) dysfunction and we have recently shown that FD patients have a dysbiotic gut microbiome and altered metabolome. These findings were recapitulated in an FD mouse model and moreover, the FD mice had reduced intestinal motility, as did patients. To understand the cellular basis for impaired GI function in FD, the enteric nervous system (ENS; both female and male mice) from FD mouse models was analyzed during embryonic development and adulthood. We show here that not only is Elp1 required for the normal formation of the ENS, but it is also required in adulthood for the regulation of both neuronal and non-neuronal cells and for target innervation in both the mucosa and in intestinal smooth muscle. In particular, CGRP innervation was significantly reduced as was the number of dopaminergic neurons. Examination of an FD patient's gastric biopsy also revealed reduced and disoriented axons in the mucosa. Finally, using an FD mouse model in which Elp1 was deleted exclusively from neurons, we found significant changes to the colon epithelium including reduced E-cadherin expression, perturbed mucus layer organization, and infiltration of bacteria into the mucosa. The fact that deletion of Elp1 exclusively in neurons is sufficient to alter the intestinal epithelium and perturb the intestinal epithelial barrier highlights a critical role for neurons in regulating GI epithelium homeostasis.

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestines without a cure. Current therapies suppress inflammation to prevent further intestinal damage. However, healing already damaged intestinal epithelia is still an unmet medical need. Under physiological conditions, Lgr5+ intestinal stem cells (ISCs) in the intestinal crypts replenish the epithelia every 3-5 days. Therefore, understanding the regulation of Lgr5+ ISCs is essential. Previous data suggest vitamin D signaling is essential to maintain normal Lgr5+ ISC function in vivo. Our recent data indicate that to execute its functions in the intestines optimally, 1,25(OH)2D requires high concentrations that, if present systemically, can cause hypercalcemia (i.e., blood calcium levels significantly higher than physiological levels), leading to severe consequences. Using 5-bromo-2'-deoxyuridine (BrdU) to label the actively proliferating ISCs, our previous data suggested that de novo synthesized locally high 1,25(OH)2D concentrations effectively enhanced the migration and differentiation of ISCs without causing hypercalcemia. However, although sparse in the crypts, other proliferating cells other than Lgr5+ ISCs could also be labeled with BrdU. This current study used high-purity Lgr5+ ISC lines and a mouse strain, in which Lgr5+ ISCs and their progeny could be specifically tracked, to investigate the effects of de novo synthesized locally high 1,25(OH)2D concentrations on Lgr5+ ISC function. Our data showed that 1,25(OH)2D at concentrations significantly higher than physiological levels augmented Lgr5+ ISC differentiation in vitro. In vivo, de novo synthesized locally high 1,25(OH)2D concentrations significantly elevated local 1α-hydroxylase expression, robustly suppressed experimental colitis, and promoted Lgr5+ ISC differentiation. For the first time, this study definitively demonstrated 1,25(OH)2D's role in Lgr5+ ISCs, underpinning 1,25(OH)2D's promise in IBD therapy.

The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.

Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1β, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota's diversity and balance.

Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN.

This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed.

There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(β -24.9, 95%CI -39.0 to -10.7,p < 0.001).

EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible.

IV.

A significant association between atopic dermatitis and leaky gut syndrome has been demonstrated in humans. No studies have been conducted to determine whether there is an association between atopic dermatitis and intestinal damage in dogs.

This study aimed to determine whether there is an association between canine atopic dermatitis and intestinal damage using selected intestinal-related biomarkers.

Twenty-six dogs with atopic dermatitis and 10 healthy dogs were included. Moderate-to-severe pruritus, erythema, erosion and alopecia on different parts of the body were sought in dogs to suspect atopic dermatitis. The presence of atopic dermatitis was confirmed by an allergic skin test. Serum biomarkers including intestinal fatty acid binding protein (I-FABP), intestinal alkaline phosphatase (IAP), trefoil factor-3 (TFF-3), immunoglobulin E (IgE), interleukin-4 (IL-4) and interleukin-13 (IL-13) concentrations were measured from venous blood samples.

Of the 26 dogs tested for allergens, 16 were found to be sensitive to mould mites, 10 to vernal grass, eight to house dust mites, five to wheat dust and five to grass pollen mix allergens. Significant increases in serum IAP, TFF-3, IgE, IL-4 and IL-13 concentrations were determined.

It was thought that the increase in TFF-3 and IAP concentrations may be due to the presence of intestinal epithelial damage and the repair of this damage. In addition, the development of atopic dermatitis may be predisposed to the entry of allergens into the body through sites of intestinal damage.

Despite the potential health risks associated with feeding raw and non-traditional diets, the use of these diets in dogs is increasing, yet the health outcomes associated with these diets is not well understood. This study investigates the effect of feeding dogs a kibble or raw meat-based diets on fecal microbiota composition, serum metabolomics and inflammatory markers.

Clinically healthy dogs with a history of consuming either kibble (KD, n = 27) or raw meat-based diets (RMBD, n = 28) for more than 1 year were enrolled. Dogs were fed a standardized diet of either a single brand of KD or RMBD for 28 days. Serum and fecal samples were collected for analysis of microbiota, metabolomics, and inflammatory markers. Multiple regression analysis was performed for each of the metabolites and inflammatory markers, with feed group, age and BCS included as independent variables.

The fecal microbiota composition differed between the KD and RMBD groups. Beta-diversity and some indices of alpha-diversity (i.e., Shannon and Simpson) were different between the two diet groups. Sixty- three serum metabolites differed between KD and RMBD-fed dogs with the majority reflecting the differences in macronutrient composition of the two diets.Fecal IAP, IgG and IgA were significantly higher in RMBD dogs compared to KD dogs, while systemic markers of inflammation, including serum c-reactive protein (CRP), galectin, secretory receptor of advanced glycation end-products (sRAGE), haptoglobin, and serum IgG were similar in dogs fed either diet.

Diet composition significantly affected fecal microbiota composition and metabolome. Although it had a potentially beneficial effect on local inflammatory markers, feeding RMBD had no impact on systemic inflammation. The influence of these changes on long term health outcomes provides an area for future study.

Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, is one of the essential modulators of host responses to inflammation. In this study, we evaluate the putative protective effect of AAT against MODS and mortality in a mouse model of polymicrobial abdominal sepsis.

Polymicrobial abdominal sepsis was induced in C57BL/6N mice by cecal ligation and puncture (CLP). Immediately after CLP surgery, mice were treated intraperitoneally with three different forms of human AAT-plasma-derived native (nAAT), oxidized nAAT (oxAAT), or recombinant AAT (recAAT)-or were injected with vehicle. Sham-operated mice served as controls. Mouse survival, bacterial load, kidney and liver function, immune cell profiles, cytokines/chemokines, and free (labile) heme levels were assessed. In parallel, in vitro experiments were carried out with resident peritoneal macrophages (MPMΦ) and mouse peritoneal mesothelial cells (MPMC).

All AAT preparations used reduced mortality in septic mice. Treatment with AAT significantly reduced plasma lactate dehydrogenase and s-creatinine levels, vascular leakage, and systemic inflammation. Specifically, AAT reduced intraperitoneal accumulation of free heme, production of cytokines/chemokines, and neutrophil infiltration into the peritoneal cavity compared to septic mice not treated with AAT. In vitro experiments performed using MPMC and primary MPMΦ confirmed that AAT not only significantly decreases lipopolysaccharide (LPS)-induced pro-inflammatory cell activation but also prevents the enhancement of cellular responses to LPS by free heme. In addition, AAT inhibits cell death caused by free heme in vitro.

Data from the septic CLP mouse model suggest that intraperitoneal AAT treatment alone is sufficient to improve sepsis-associated organ dysfunctions, preserve endothelial barrier function, and reduce mortality, likely by preventing hyper-inflammatory responses and by neutralizing free heme.

The intestinal barrier is critical for maintaining intestinal homeostasis, and its dysfunction is associated with various diseases. Recent findings have revealed the multifunctional role of intestinal alkaline phosphatase (IAP) in diverse biological processes, including gut health maintenance and function. This review summarizes the protective effects of IAP on intestinal barrier integrity, encompassing the physical, chemical, microbial, and immune barriers. We discuss the results and insights from in vitro, animal model, and clinical studies as well as the available evidence regarding the impact of diet on IAP activity and expression. IAP can also be used as an indicator to assess intestinal-barrier-related diseases. Further research into the mechanisms of action and long-term health effects of IAP in maintaining overall intestinal health is essential for its future use as a dietary supplement or functional component in medical foods.

Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery.

Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS.

Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009).

Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.

Pectin, a type of soluble fiber, promotes morphological changes in the small intestinal villi. Although its physiological significance is unknown, we hypothesized that changes in villus morphology enhance the efficiency of nutrient absorption in the small intestine and investigated the effect of pectin derived from persimmon on calcium absorption using polarized Caco-2 cells. In polarized Caco-2 cells, pectin altered the mRNA expression levels of substances involved in calcium absorption and the regulation of intracellular calcium concentration and significantly reduced calcium absorption. Although this was comparable to the results of absorption and permeability associated with the addition of active vitamin D, the simultaneous action of pectin and active vitamin D did not show any additive effects. Furthermore, as active vitamin D significantly increases the activity of intestinal alkaline phosphatase (ALP), which is known to be involved in the regulation of intestinal absorption of calcium and lipids, we also investigated the effect of pectin on intestinal ALP activity. As a result, it was found that, unlike the effect of active vitamin D, pectin significantly reduced intestinal ALP activity. These results suggest that pectin stimulates polarized Caco-2 cells through a mechanism distinct from the regulation of calcium absorption by vitamin D, modulating total calcium absorption from the elongated villi through morphological changes in the small intestine by suppressing it at the cellular level.

To provide prominent accessibility of fishmeal to the European population, the currently available, time- and cost-extensive feeding trials, which evaluate fish feed, should be replaced. The current paper reports on the development of a novel 3D culture platform, mimicking the microenvironment of the intestinal mucosa in vitro. The key requirements of the model include sufficient permeability for nutrients and medium-size marker molecules (equilibrium within 24 h), suitable mechanical properties (G' < 10 kPa), and close morphological similarity to the intestinal architecture. To enable processability with light-based 3D printing, a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink is developed and combined with Tween 20 as porogen to ensure sufficient permeability. To assess the permeability properties of the hydrogels, a static diffusion setup is utilized, indicating that the hydrogel constructs are permeable for a medium size marker molecule (FITC-dextran 4 kg mol-1 ). Moreover, the mechanical evaluation through rheology evidence a physiologically relevant scaffold stiffness (G' = 4.83 ± 0.78 kPa). Digital light processing-based 3D printing of porogen-containing hydrogels results in the creation of constructs exhibiting a physiologically relevant microarchitecture as evidenced through cryo-scanning electron microscopy. Finally, the combination of the scaffolds with a novel rainbow trout (Oncorhynchus mykiss) intestinal epithelial cell line (RTdi-MI) evidence scaffold biocompatibility.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day +7 and +30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an L:R ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. L:R ratios were increased at day +7 but returned to baseline at day +30 in most patients (P = .014). Conditioning regimen intensity did not affect the trajectory of L:R (P = .39). Baseline L:R ratios did not vary with diagnosis. L:R correlated with LBP levels (r2 = 0.208; P = .0014). High L:R ratios were associated with lower microbiome diversity (P = .035), loss of anaerobic organisms (P = .020), and higher plasma LBP (P = .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through L:R ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.

Although gut inflammation and dysbiosis have been implicated in the pathophysiology of severe cases of coronavirus disease 2019 (COVID-19), the role of intestinal anti-inflammatory enzymes, such as alkaline phosphatase, is still underexplored. Therefore, the aim of this study was to compare intestinal alkaline phosphatase (iALP) activity and its proinflammatory substrate - bacterial lipopolysaccharide (LPS) - concentration between mild-to-moderate and severe COVID-19 patients.

Stool samples collected from 53 mild-to-moderate and 57 severe adult COVID-19 patients, previously enrolled in a national multicentre cross-sectional study (NCT04355741), were analysed for iALP activity and LPS concentration.

iALP activity decreased by 40% in severe compared to mild-to-moderate COVID-19 patients (median [interquartile range] of 120.6 [25.2-593.1] nmol pNP/min/g of protein vs 202.8 [102.1-676.1] nmol pNP/min/g of protein; P = .04) after adjustment for clinical and gut microbiota parameters. Regarding fecal LPS, its concentration was found to be decreased in severe patients (mean ± standard error of mean of 18,118 ± 1225 EU/g of feces vs 22,508 ± 1203 EU/g of feces; P = .01), although this parameter did not correlate with plasma levels of C-reactive protein (P = .08), a sensitive biomarker of systemic inflammation. In contrast, fecal ALP activity / LPS concentration ratio, an indicator of iALP efficiency, was found to be increased in severe compared to mild-to-moderate COVID-19 patients (P = .04).

Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis (eg inflammation and dysbiosis) associated with COVID-19 severity.

We conducted an umbrella review to summarize the existing evidence on the effect of early enteral nutrition (EEN) compared with other approaches, including delayed enteral nutrition (DEN), parenteral nutrition (PN), and oral feeding (OF) on clinical outcomes in hospitalized patients. We performed a systematic search up to December 2021, in MEDLINE (via PubMed), Scopus, and Institute for Scientific Information Web of Science. We included systematic reviews with meta-analyses (SRMAs) of randomized trials investigating EEN compared with DEN, PN, or OF for any clinical outcomes in hospitalized patients. We used "A Measurement Tool to Assess Systematic Reviews" (AMSTAR2) and the Cochrane risk-of-bias tool for assessing the methodological quality of the systematic reviews and their included trial, respectively. The certainty of the evidence was rated using the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. We included 45 eligible SRMAs contributing with a total of 103 randomized controlled trials. The overall meta-analyses showed that patients who received EEN had statistically significant beneficial effects on most outcomes compared with any control (ie, DEN, PN, or OF), including mortality, sepsis, overall complications, infection complications, multiorgan failure, anastomotic leakage, length of hospital stay, time to flatus, and serum albumin levels. No statistically significant beneficial effects were found for risk of pneumonia, noninfectious complications, vomiting, wound infection, as well as number of days of ventilation, intensive care unit days, serum protein, and pre-serum albumin levels. Our results indicate that EEN may be preferred over DEN, PN, and OF because of the beneficial effects on many clinical outcomes.

Conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr-/- mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicked the dyslipidemia and atherosclerosis induced by feeding a Western diet (WD). Here, we report that adding unsaturated LPA to standard mouse chow also increased the content of reactive oxygen species and oxidized phospholipids (OxPLs) in jejunum mucus. To determine the role of intestinal autotaxin, enterocyte-specific Ldlr-/-/Enpp2 KO (intestinal KO) mice were generated. In control mice, the WD increased enterocyte Enpp2 expression and raised autotaxin levels. Ex vivo, addition of OxPL to jejunum from Ldlr-/- mice on a chow diet induced expression of Enpp2. In control mice, the WD raised OxPL levels in jejunum mucus and decreased gene expression in enterocytes for a number of peptides and proteins that affect antimicrobial activity. On the WD, the control mice developed elevated levels of lipopolysaccharide in jejunum mucus and plasma, with increased dyslipidemia and increased atherosclerosis. All these changes were reduced in the intestinal KO mice. We conclude that the WD increases the formation of intestinal OxPL, which i) induce enterocyte Enpp2 and autotaxin resulting in higher enterocyte LPA levels; that ii) contribute to the formation of reactive oxygen species that help to maintain the high OxPL levels; iii) decrease intestinal antimicrobial activity; and iv) raise plasma lipopolysaccharide levels that promote systemic inflammation and enhance atherosclerosis.

Vitamin D insufficiency induces calcification disorder of bone or a decrease in bone mineral density, increasing the risk of fracture. Alkaline phosphatase (ALP) activity, a differentiation marker for intestinal epithelial cells, is regulated by vitamin D. It has also been suggested that ALP may prevent metabolic endotoxemia by dephosphorylating lipopolysaccharide. We hypothesized that vitamin D restriction and/or a high-fat diet influences ALP activity in each tissue and serum lipopolysaccharide concentrations and increases the risk of metabolic endotoxemia. Eleven-week-old female rats were divided into 4 groups: basic control diet (Cont.), basic control diet with vitamin D restriction (DR), high-fat diet (HF), and high-fat diet with vitamin D restriction (DRHF) groups. They were acclimated for 28 days. The results of 2-way analysis of variance showed that intestinal ALP activity, which may contribute to an improvement in phosphate/lipid metabolism and longevity, in the high-fat diet groups (HF and DRHF) was higher than in the low-fat diet groups (Cont. and DR). ALP activity in the vitamin D-restricted groups (DR and DRHF) was lower than in the vitamin D-sufficient groups (Cont. and HF). Furthermore, serum endotoxin concentrations were significantly higher in the high-fat diet groups (HF and DRHF) than in the low-fat diet groups (Cont. and DR). In the vitamin D-restricted groups (DR and DRHF), serum endotoxin concentrations were also significantly higher than in the vitamin D-sufficient groups (Cont. and HF). These results suggest that vitamin D restriction and/or a high-fat diet increases the risk of metabolic endotoxemia.

We recently reported that fermentable nondigestible carbohydrates such as oligosaccharides, commonly increase colonic alkaline phosphatase (ALP) activity and the gene expression of Alpi-1, coding for rat intestinal alkaline phosphatase-I isozyme in rats and that the effect of oligosaccharides on colonic ALP activity is affected by the quality of dietary fats. We hypothesized that the amount of dietary fat would modulate the effect of oligosaccharides on colonic ALP and luminal environment in rats. In experiment 1, male Sprague-Dawley rats were fed a low-fat (LF, 5% lard) or high-fat (HF, 30% lard) diet with or without 4% fructo-oligosaccharides (FOS). In experiment 2, they were fed a 2.5%, 7%, 20%, or 40% fat (lard) diet with 4% FOS for 2 weeks. Dietary FOS in the HF diet (HF-FOS) significantly increased ALP activity in the colon and cecal digesta and colonic expression of Alpi-1, but not in the LF diet with FOS groups (LF-FOS). In comparison to the LF-FOS group, the increases in fecal mucins, Lactobacillus ratio, as well as cecal n-butyrate, and the decrease in fecal Clostridium coccoides, were more pronounced in the HF-FOS group. Compared with the 2.5% or 7% fat + FOS diet, the 20% fat + FOS diet significantly increased colonic ALP activity, Alpi-1 expression, and fecal mucins. These factors did not differ significantly between 20% and 40% fat + FOS diets. To exert the maximum effect of FOS on the colonic luminal environment, including ALP activity in rats, significantly more fat may be required than that contained present a LF diet.

As cells of innate immunity, macrophages are a class of innate immune cells existing in almost all tissues and play a crucial role in bone repair. However, it remains a challenge to modulate the sequential activation of the deferent phenotypes in macrophage when designing the titanium (Ti) implants. In this study, the Mg-Fe layered double hydroxides (LDHs) was coated on Ti substrate through hydrothermal treatment. Further on lipopolysaccharide (LPS) was introduced onto the LDHs through adsorption and ions exchange. The adsorption efficiency of the coating on LPS reached 72.8% in 24 h due to the anion exchange and electrostatic interactions between the LPS and the LDH layers in deionized water. The LDHs-LPS coating released a large amount of LPS in the early stage, which induced macrophages into M1 phenotype via activating TLR-4 → MyD88 and TLR-4 → Ticam-1/2 signal pathways. Subsequently, the M1 macrophages were transformed into M2 phenotype by regulating the integrin α5β1 of cells by the nanostructures, wetting angle and Mg²⁺ of the coating. The LDHs-LPS coating endows Ti with the ability of stage immunomodulation, indicating the positive osteoimmunomodulatory property.

Probiotics such as Lactobacillus spp. could modulate the intestinal microbiota composition, supporting gastrointestinal tract barrier function and benefiting human health. To evaluate the anticancer and probiotic properties of potentially active autochthonous Lacticaseibacillus paracasei strains on proliferating and differentiated enterocytes, human colon adenocarcinoma cell line HT29 was used as a model. The lactic acid bacteria (LAB) were isolated from new ecological niches—mountain anthills populated by redwood ants (Formica rufa L.). Human colorectal adenocarcinoma cells (HT29, ATCC, HTB-38™) were treated for twenty-four hours with supernatants (SNs) derived from four strains of Lacticaseibacillus paracasei: P4, C8, C15 and M2.1. An MTT assay, alkaline phosphatase activity, IAP, Bax and Bcl-2 gene expression analysis (RT-qPCR) and the Bax/Bcl-2 ratio were evaluated. The MTT assay revealed that the observed effects varied among groups. However, 10% neutralized supernatants from P4, C8, C15 and M2.1 strains did not show cytotoxic effects. In contrast to non-differentiated cells, a significant (p < 0.001) rise in ALP activity in all treatments, with an average of 18%, was established in differentiated cells. The IAP expression was remarkably downregulated in the differentiated M2.1 group (p < 0.05) and upregulated in the non-differentiated P4 (p < 0.05) and M2.1 (p < 0.05) groups. The Bax/Bcl-2 quantity expression ratio in P4 was significantly (p < 0.05) upregulated in proliferating cancer cells, but in P4- and M2.1-differentiated cells these values were downregulated (p < 0.05). The obtained results indicate that the isolated L. paracasei strains possess anticancer and probiotic properties and could be used as additives for functional dairy foods and thus benefit human health.

As an important metal in industry, national defense, and production, nickel widely exists in nature and is also a necessary trace element for human beings and animals. Nickel deficiency will affect the growth and development of animals, the contents of related active substances, enzymes and other essential elements in vivo. However, excessive nickel or longer nickel exposure can induce excessive free radicals (reactive oxygen species and reactive nitrogen) in the body, which can lead to a variety of cell damage, apoptosis and canceration, and ultimately pose negative effects on the health of the body. Among them, the intestinal tract, as the largest interface between the body and the external environment, greatly increases the contact probability between nickel or nickel compounds and the intestinal mucosal barrier, thus, the intestinal structure and function are also more vulnerable to nickel damage, leading to a series of related diseases such as enteritis. Therefore, this paper briefly analyzed the damage mechanism of nickel or its compounds to the intestinal tract from the perspective of four intestinal mucosal barriers: mechanical barrier, immune barrier, microbial barrier and chemical barrier, we hope to make a certain theoretical contribution to the further research and the prevention and treatment of nickel related diseases.

Intestinal-type alkaline phosphatase (IAP) is expressed at a high concentration in the brush border membrane of intestinal epithelial cells and is known to be a gut mucosal defense factor. In humans, a single gene (ALPI) for IAP has been isolated, and its transcription produces two kinds of alternatively spliced mRNAs (aAug10 and bAug10). Recently, we discovered that vitamin D up-regulated the expression of both types of human IAP alternative splicing variants in Caco-2 cells. However, the functional difference of protein encoded by the mRNA variants has remained elusive. In the present study, we aimed to provide further insight into the characterization and structure of IAP isoforms. To analyze the protein translated from the ALPI gene, we constructed two kinds of cDNA expression plasmids (aAug10 and bAug10), and the transfected cells were homogenized and assayed for alkaline phosphatase (ALP) activity. We also designed the homology-modeled 3D structures of the protein encoded by the mRNA variants (ALPI-aAug10 and ALPI-bAug10). The levels of ALP activity of COS-1 cells transfected with the aAug10 plasmid were increased significantly, while cells transfected with the bAug10 plasmid had undetectable ALP activity. The homology-modeled 3D structures revealed that the variant bAug10 lacks the central N-terminal α-helix and residue corresponding to Asp-42 of ALPI-aAug10 near the active site. This is the first report on the characterization and structure of alternatively spliced transcript variants of the human ALPI gene. Further studies on the regulation of aAug10 and/or bAug10 mRNA expression may identify novel physiological functions of IAP.

This study aims to investigate the influence of adding Lonicera japonica (L. japonica) and Radix Puerariae crude extracts and their mixture to the diet of finishing pigs on their fecal microbes and nutrient apparent digestibility. A total of 72 healthy Duroc × Landrace × Yorkshire crossbred barrows without significant differences in body weight (93 ± 2 kg) were selected and randomly divided into four groups (18 in each group). Three replicate pens per group (six pigs per pen) were used, and two pigs were evaluated for each pen. The groups were fed the following diets: control group (CON), basic diet; chlorogenic acid group (CGA group), basic diet + 1 kg/ton L. japonica crude extract; Pueraria flavonoid group (PF group), basic diet + 1 kg/ton Radix Puerariae crude extract; and mix group (Mix group), basic diet + 0.5 kg/ton L. japonica crude extract + 0.5 kg/ton Radix Puerariae crude extract. The following results were obtained: (1) At the phylum level, Bacteroidetes, Firmicutes, Spirochaetes, Proteobacteria, Fibrobaeteres, and Kiritimatiellaeota were the main components of the fecal microbiota (top 5); the relative abundance of bacteria from phyla Firmicutes significantly increased in the Mix group than in the CON group (p < 0.05). At the genus level, Treponema_2, Rikenellaceae_RC9_gut_group, uncultured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Prevotellaceae, and Prevotellaceae_NK3B31_group were the main components of the fecal microbiota (top 5); the relative abundance of bacteria from genus Lactobacillus significantly increased in the Mix group than in the CON group (p < 0.05). Chao1 and Ace counts were significantly higher in group CGA than in the CON group and group Mix (p < 0.05). The alpha and beta diversities and the relative abundance of fecal microbes were higher in all test groups than in the CON group. (2) The protein digestibility was significantly higher in the CGA and PF groups than in the CON group, and the TP digestibility was significantly higher in the CGA than in the CON and Mix groups (p < 0.05). In conclusion, Lonicera japonica and Radix Puerariae crude extract supplementation in the diet significantly changed fecal microbiota and improved the protein and TP digestibility of finishing pigs.

The importance of intestinal alkaline phosphatase (IAP) in maintaining gut health and intestinal homeostasis is well established. The objective of this study was to investigate the tolerance of poultry and swine to dietary supplementation of a novel microbial-derived alkaline phosphatase (AP; E.C. 3.1.3.1 produced by Paenibacillus lentus strain CMG3709). Studies were conducted on day-old Ross 308 chicken (n = 1,000; Study 1) and weaned piglets (n = 180; Study 2) for a duration of 42 d; and consisted of four treatment groups (TG) based on the concentration of microbial-derived AP supplemented in their diet at 0; 12,000; 20,000; and 200,000 U/kg of feed. Parameters such as animal survival, hematology, coagulation, and biochemical indices were assessed at the end of the study. The effect of microbial AP on nutrient absorption through skin pigmentation and intestinal permeability were also investigated in broilers (n = 600; Study 3). In poultry (Study 1), there were no statistically significant differences between control and TG for any of the hematological and biochemical parameters, except for a marginal increase (P < 0.05) in serum phosphorus at the highest dose. This variation was not dose-dependent, was well within the reference range, and was not associated with any clinical correlates. In swine (Study 2), hematological parameters such as leukocyte, basophil, and lymphocyte counts were lower (P < 0.05) for the two highest doses but were traced back to individual variations within the group. The biochemical indices in piglets showed no significant differences between control and supplemental groups except for glucose (P = 0.0005), which showed a high effect (P = 0.008) of the random blood collection order. Nonetheless, glucose was within the normal reference range, and were not related to in-feed supplementation of AP as they had no biological significance. The survival rate in all three studies was over 98%. Dietary supplementation of microbial-derived AP up to 16.7 times the intended use (12,000 U/kg feed) level had no negative effects in both poultry and swine. In-feed supplementation of microbial-derived AP for 28 d improved intestinal pigment absorption (P < 0.0001) and reduced intestinal paracellular permeability (P = 0.0001) in broilers (Study 3). Based on these results, it can be concluded that oral supplementation of microbial-derived AP is safe for poultry and swine and effective at improving gut health in poultry.

This study compared the nutrient-energy retention, digestive function, growth performance, and welfare of rainbow trout (ibw 54 g) fed isoproteic (42%), isolipidic (24%), fishmeal-free diets (CV) over 13 weeks. The diets consisted of plant-protein replacement with graded levels (10, 30, 60%) of protein from poultry by-product (PBM) and black soldier fly H. illucens pupae (BSFM) meals, either singly or in combination. A fishmeal-based diet was also tested (CF). Nitrogen retention improved with moderate or high levels of dietary PBM and BSFM relative to CV (p < 0.05). Gut brush border enzyme activity was poorly affected by the diets. Gastric chitinase was up-regulated after high BSFM feeding (p < 0.05). The gut peptide and amino acid transport genes were differently regulated by protein source and level. Serum cortisol was unaffected, and the changes in metabolites stayed within the physiological range. High PBM and high BSFM lowered the leukocyte respiratory burst activity and increased the lysozyme activity compared to CV (p < 0.05). The BSFM and PBM both significantly changed the relative percentage of lymphocytes and monocytes (p < 0.05). In conclusion, moderate to high PBM and BSFM inclusions in fishmeal-free diets, either singly or in combination, improved gut function and nutrient retention, resulting in better growth performance and the good welfare of the rainbow trout.

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease that includes ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis of IBD is not fully understood but is most reported associated with immune dysregulation, dysbacteriosis, genetic susceptibility, and environmental risk factors. Vitamin D is an essential nutrient for the human body, and it not only regulates bone metabolism but also the immune system, the intestinal microbiota and barrier. Vitamin D insufficiency is common in IBD patients, and the abnormal low levels of vitamin D are highly correlated with disease activity, treatment response, and risk of relapse of IBD. Accumulating evidence supports the protective role of vitamin D in IBD through regulating the adaptive and innate immunity, maintaining the intestinal barrier and balancing the gut microbiota. This report aims to provide a broad overview of the role vitamin D in the immune system, especially in the pathogenesis and treatment of IBD, and its possible role in predicting relapse.

Emerging studies have shown that gut-derived endotoxins might play a role in intestinal and systemic inflammation. Although the significance of intestinal permeability in modulating the pathogenesis of Schizophrenia (SCZ) is recognized, not much data on the specific role of intestinal permeability biomarkers, viz., zonulin, lipopolysaccharide-binding protein (LBP), and intestinal alkaline phosphatase (IAP) in SCZ is available. Therefore, we measured the plasma levels of zonulin, LBP, and IAP and its correlation with neutrophil-to-lymphocyte ratio (NLR); a marker of systemic inflammation in patients with SCZ.

We recruited 60 individuals, patients with SCZ (n = 40) and healthy controls (n = 20), from a large tertiary neuropsychiatry center. Plasma levels of zonulin, IAP, and LBP were quantified by enzyme-linked immunosorbent assay.

Plasma levels of both LBP and zonulin were significantly increased (P <0.05), whereas the IAP levels (P <0.05) were significantly decreased in patients with SCZ compared to healthy controls. Pearson correlation analysis revealed that zonulin and LBP had a significant positive correlation with NLR, and IAP negatively correlated with NLR. Individuals with SCZ had higher independent odds of zonulin [odds ratio (OR): 10.32, 95% CI: 1.85-57.12], LBP [OR: 1.039, 95% CI: 1.02-1.07], and IAP [OR: 0.643, 95% CI: 0.471-0.879], even after adjusting for potential confounders.

Our study demonstrates an association of zonulin, LBP, and IAP in Asian Indian SCZ patients and correlates with NLR. Our results indicate that low-grade inflammation induced by metabolic endotoxemia might be implicated in the pathoetiology of SCZ.