The study investigates the strain-specific immunomodulatory properties of live and thermally-inactivated (TI) lactic acid bacteria (LAB) derived from traditional Polish fermented foods, focusing on their potential as probiotics and postbiotics. LAB strains, known for their role in food fermentation, were assessed for their ability to influence cytokine production in THP-1 macrophages, maintain intestinal epithelial barrier integrity in Caco-2 monolayers, exhibit antioxidant activity, and produce specific organic acids and sugars. The research demonstrated that live LAB strains significantly upregulated the anti-inflammatory cytokine IL-10, particularly under inflammatory conditions, while TI strains exhibited notable antioxidant and anti-inflammatory properties. TI strains showed a greater ability to protect epithelial barrier function and reduce pro-inflammatory cytokine secretion than live strains, suggesting a promising role for postbiotics. The findings underscore the potential of LAB from fermented foods, demonstrating that postbiotic derivatives can differently influence inflammation compared to live bacteria, highlighting their potential as immune-enhancing agents, capable of modulating immune responses and offering therapeutic benefits against inflammation-related disorders. However, the limitations of in vitro models highlight the need for further in vivo and clinical studies to validate these effects and fully uncover the health benefits of these LAB strains for humans.

We explored the mechanisms underlying the improvement of postoperative ileus (POI) following probiotic pretreatment. We assessed intestinal permeability, inflammation, tight junction (TJ) protein expression in the gut epithelium, and plasma interleukin (IL)-17 levels in a guinea pig model of POI.

Guinea pigs were divided into control, POI, and probiotic groups. The POI and probiotic groups underwent surgery, but the probiotic group received probiotics before the procedure. The ileum and proximal colon were harvested. Intestinal permeability was measured via horseradish peroxidase permeability. Inflammation was evaluated via leukocyte count in the intestinal wall muscle layer, and calprotectin expression in each intestinal wall layer was analyzed immunohistochemically. TJ proteins were analyzed using immunohistochemical staining, and plasma IL-17 levels were measured using an enzyme-linked immunosorbent assay.

The POI group exhibited increased intestinal permeability and inflammation, whereas probiotic pretreatment reduced the extent of these POI-induced changes. Probiotics restored the expression of TJ proteins occludin and zonula occludens-1 in the proximal colon, which were increased in the POI group. Calprotectin expression significantly increased in the muscle layer of the POI group and was downregulated in the probiotic group; however, no distinct differences were observed between the mucosal and submucosal layers. Plasma IL-17 levels did not significantly differ among the groups.

Probiotic pretreatment may relieve POI by reducing intestinal permeability and inflammation and TJ protein expression in the gut epithelium. These findings suggest a potential therapeutic approach for POI management.

Despite being classified as neurodevelopmental disorders, in recent years, there has been a growing interest in the association between autism spectrum disorders (ASDs) and gut pathology. This comprehensive and systematic review explores a potential mechanism underlying gut pathology in ASDs, including alterations in gut microbiota, intestinal permeability, immune dysregulation, and gastrointestinal (GI) symptoms. Specifically, it delves into the role of toxic and essential metals and their interplay, affecting the development and function of the GI tract. The review also discusses the potential implications of this gut pathology in the development and management of ASDs. Studies have shown that heavy metal exposure, whether through environmental sources or dietary intake, can disrupt the delicate balance of trace elements in the gut. This disruption can adversely affect zinc homeostasis, potentially exacerbating gut pathology in individuals with ASDs. The impaired zinc absorption resulting from heavy metal exposure may contribute to the immune dysregulation, oxidative stress, and inflammation observed in the gut of individuals with ASDs. By shedding light on the multifaceted nature of gut pathology, including the impact of metal dyshomeostasis as a non-genetic factor in ASD, this review underscores the significance of the gut-brain axis in the etiology and management of ASDs.

Huntington's disease (HD) is a currently incurable neurogenerative disorder and is typically characterized by progressive movement disorder (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which is depression), and peripheral symptoms (including gastrointestinal dysfunction). There are currently no approved disease-modifying therapies available for HD, with death usually occurring approximately 10-25 years after onset, but some therapies hold promising potential. HD subjects are often burdened by chronic diarrhea, constipation, esophageal and gastric inflammation, and a susceptibility to diabetes. Our understanding of the microbiota-gut-brain axis in HD is in its infancy and growing evidence from preclinical and clinical studies suggests a role of gut microbial population imbalance (gut dysbiosis) in HD pathophysiology. The gut and the brain can communicate through the enteric nervous system, immune system, vagus nerve, and microbiota-derived-metabolites including short-chain fatty acids, bile acids, and branched-chain amino acids. This review summarizes supporting evidence demonstrating the alterations in bacterial and fungal composition that may be associated with HD. We focus on mechanisms through which gut dysbiosis may compromise brain and gut health, thus triggering neuroinflammatory responses, and further highlight outcomes of attempts to modulate the gut microbiota as promising therapeutic strategies for HD. Ultimately, we discuss the dearth of data and the need for more longitudinal and translational studies in this nascent field. We suggest future directions to improve our understanding of the association between gut microbes and the pathogenesis of HD, and other 'brain and body disorders'.

The intestinal dysfunction plays an important role in the decreased growth performance of broiler chickens under high stocking density. Gut microbiota plays an important role in maintaining intestinal health. However, the modulation pathway of gut microbiota by regulating the intestinal barrier and histomorphology remains unknown.

One hundred and forty-four male Arbor Acres broilers (22-d-old) with similar weight were randomly assigned to two treatments: a high (HSD, 20 broilers/m2) or low stocking density treatment (LSD, 14 broilers/m2), with six replicates per treatment. The experimental period was 20 days, from 22 to 42 days of age.

The final body weight at 42 days of age was lower in the HSD group (P = 0.0013) and average daily feed intake (P = 0.016) and weight gain of broilers from 22 to 42 days decreased (P = 0.012). In the HSD group on day 42, villus height and the ratio of villus height to the crypt depth in the ileum decreased (P < 0.05); mRNA expression of tight junction proteins, occludin (P < 0.01) and ZO1 (P < 0.05), were downregulated; whereas IL-6, TNFα, and NFκB p65 (P < 0.05) and IL-1β (P < 0.01) were upregulated. The HSD treatment increased the relative abundance of Lactobacillus (P = 0.045) and decreased that of Alistipes (P = 0.031). Cecal concentrations of acetic (P < 0.05) and butyric acids (P < 0.05) decreased. Gut metabolites co-metabolized by the host and gut microbiota were altered in the HSD group, with decreases in glycerophospholipid and tryptophan metabolites negatively correlated with Lactobacillus (P < 0.05). The metabolite content of conjugated bile acids decreased and free bile acids increased (P < 0.05) with HSD. Bile salt hydrolase (BSH) was increased in the intestine of HSD-treated broilers (P < 0.01). The total cholic acid content of the HSD group was lower in the jejunum and ileum (P < 0.05) but higher in the cecum than in the LSD group (P < 0.01).

HSD caused dysbiosis of the intestinal microbiota such as increased Lactobacillus, along with enhanced BSH activity and excessive unabsorbed free bile acids. This resulted in ileal epithelial cells damage, inflammation, decreased growth performance of broilers under high stocking densities.

The gut microbiome is a complex system that directly interacts with and influences many systems in the body. This delicate balance of microbiota plays an important role in health and disease and is highly influenced by lifestyle factors and the surrounding environment. As further research emerges, understanding the full potential of the gut microbiome and the impact of using nutraceuticals to positively influence its function may open the door to greater therapeutic outcomes in the treatment and prevention of disease. Curcumin, a bioactive compound derived from the turmeric rhizome, has been studied in depth for its influence on human health as a potent anti-inflammatory and antioxidant properties. However, the therapeutic activity of curcumin is limited by its low oral bioavailability. While most available research has primarily focused on the curcuminoid compounds of turmeric, the non-curcuminoid compounds hold promise to offer therapeutic benefits while synergistically enhancing the bioavailability of curcumin and supporting the gut microbiome. This review summarizes current knowledge of the relationship between the gut and the various systems within the body, and how dysbiosis, or disruption in the gut microbial balance, leads to inflammation and increased risk of chronic disease. The review also summarizes recent research that focuses on the bioactivity of both the curcuminoid and non-curcuminoid compounds that comprise the whole turmeric root and their synergistic role in enhancing bioavailability to support a healthy gut microbiome and promising use in the treatment and prevention of disease.

Sleep deprivation is a prevalent issue in contemporary society, with significant ramifications for both physical and mental well-being. Emerging scientific evidence illuminates its intricate interplay with the gut-brain axis, a vital determinant of neurological function. Disruptions in sleep patterns disturb the delicate equilibrium of the gut microbiota, resulting in dysbiosis characterized by alterations in microbial composition and function. This dysbiosis contributes to the exacerbation of neurological disorders such as depression, anxiety, and cognitive decline through multifaceted mechanisms, including heightened neuroinflammation, disturbances in neurotransmitter signalling, and compromised integrity of the gut barrier. In response to these challenges, there is a burgeoning interest in therapeutic interventions aimed at restoring gut microbial balance and alleviating neurological symptoms precipitated by sleep deprivation. Probiotics, dietary modifications, and behavioural strategies represent promising avenues for modulating the gut microbiota and mitigating the adverse effects of sleep disturbances on neurological health. Moreover, the advent of personalized interventions guided by advanced omics technologies holds considerable potential for tailoring treatments to individualized needs and optimizing therapeutic outcomes. Interdisciplinary collaboration and concerted research efforts are imperative for elucidating the underlying mechanisms linking sleep, gut microbiota, and neurological function. Longitudinal studies, translational research endeavours, and advancements in technology are pivotal for unravelling the complex interplay between these intricate systems.

Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest.

Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis. The major role on gut-bone axis is due to short-chain fatty acids (SCFAs). They have the ability to influence regulatory T-cell (Tregs) development and activate bone metabolism through the action of Wnt10. SCFA production may be a mechanism by which the microbial community, by increasing the serum level of insulin-like growth factor 1 (IGF-1), leads to the growth and regulation of bone homeostasis. A specific SCFA, butyrate, diffuses into the bone marrow where it expands Tregs. The Tregs induce production of the Wnt ligand Wnt10b by CD8+ T cells, leading to activation of Wnt signaling and stimulation of bone formation. At the hormonal level, the effect of the gut microbiota on bone homeostasis is expressed through the biphasic action of serotonin. Some microbiota, such as spore-forming microbes, regulate the level of serotonin in the gut, serum, and feces. Another group of bacterial species (Lactococcus, Mucispirillum, Lactobacillus, and Bifidobacterium) can increase the level of peripheral/vascular leptin, which in turn manages bone homeostasis through the action of brain serotonin.

Purpose: Radiotherapy treatments are known to alter the gut microbiota. However, little is known regarding the effect of nuclear medicine treatments on gut microbiota, and it is established that nuclear medicine is inherently different from radiotherapy. To address this knowledge gap, we conducted a prospective study to identify changes in the gut microbiota of patients treated with [131I]NaI by comparing fecal samples before and after RAIT. Methods: Fecal samples of 64 patients (37 with thyroid cancer and 27 with hyperthyroidism) with indication for RAIT were collected 2 to 3 days before treatment and 8 to 10 days post-treatment. After DNA extraction, the gut microbiota's richness, diversity, and composition were analyzed by shotgun metagenomics. In addition, LEfSe was performed to compare compositional changes in specific bacteria. Results: Gut microbiome richness and diversity remained unchanged after RAIT, with few changes in its composition identified, especially in patients with hyperthyroidism. Conclusions: This study provides a conceptual and analytical basis for increasing our understanding of the effects of radiopharmaceuticals on gut microbiota. Our preliminary results indicate that RAIT, contrary to radiotherapy, does not cause major disruptions to the human gut microbiota.

Reducing the detrimental effects of heat stress (HS) in poultry is essential to minimize production losses. The present study evaluates the effects of dietary polyphenols prepared from underutilized wood byproducts on the growth, gut health, and cecal microbiota in broilers subjected to acute heat stress (AHS). One hundred eight one-day-old Indian River broilers were fed with 0%, 0.5%, or 1% polyphenols from shredded, steam-exploded pine particles (PSPP) in their diet. On the 37th day, forty birds were equally distributed among four groups containing either a control diet at thermoneutral temperatures (NT0%) or AHS temperatures with 0% (AHS0%), 0.5% (AHS0.5%), and 1% (AHS1%) PSPP-supplemented diets. The temperature in the NT room was maintained at 21.0 °C, while, in the AHS room, it was increased to 31 °C. AHS negatively influenced performance parameters and increased rectal temperature (RT) in broilers. The AHS0% group showed a higher expression of NOX4, HSP-70, and HSP-90 genes, while the expression was lower in PSPP-supplemented birds. In the jejunum, mRNA expression of SOD was increased in all the birds under AHS compared to NT. The expression of the CLDN1 and ZO2 genes was increased in AHS0%, while that of the ZO1 and MUC2 genes was increased in PSPP-supplemented birds. HS tends to increase TLR2 and TLR4 gene expression in chickens. The significantly modified genera were Bariatricus, Sporobacter, Sporanaerobacter, and Natranaerovirga. Concludingly, AHS negatively influences the performance parameters, RT, stress, gut-health-related genes, and pathogenic penetration, but PSPP supplementation reduces its bad impact by overcoming the stress and gut-health-related genes, increasing favorable bacterial abundance and reducing pathogenic penetration in chickens.

Background: In vitro findings on the biological functions of Lycium barbarum flavonoids (LBFs) as feed additives are limited. This study aimed to explore the effects of different concentrations of LBFs on the growth performance, immune function, intestinal barrier, and antioxidant capacity of meat ducks. A total of 240 one-day-old male meat ducks were randomly allocated to four groups, each receiving a basal diet supplemented with 0 (control), 250, 500, or 1000 mg/kg of LBFs for 42 d. Results: The results showed that dietary supplementation with 500 mg/kg of LBFs resulted in a significant increase in average daily feed intake, body weight, average daily gain, and feed conversion ratio. Dietary supplementation with 500 or 1000 mg/kg of LBFs resulted in significant decreases in serum levels of D-lactic acid and lipopolysaccharide. Dietary supplementation with 500 mg/kg LBFs significantly decreased diamine oxidase activity and enhanced the activities of catalase, total antioxidant capacity, and glutathione peroxidase in the jejunal mucosa, as well as the activity of total superoxide dismutase and the content of glutathione in the ileal mucosa, while significantly lowering the content of malondialdehyde in the ileal mucosa. Dietary supplementation with 500 mg/kg LBFs significantly up-regulated the mRNA expression of genes associated with intestinal barrier function and antioxidant capacity in the jejunal and ileal mucosa, as well as the protein expression of these antioxidant genes, and led to a significant reduction in the mRNA expression of pro-apoptotic and inflammatory-related genes. Conclusions: The addition of LBFs to the diet improved the growth performance, intestinal barrier function, immune response, and antioxidant capacity of the ducks, which may be closely associated with the activation of the Nrf2 signaling pathway and the inhibition of the NF-κB signaling pathway. The optimal dietary inclusion level of LBFs in ducks was 500 mg/kg.

The human bowel is exposed to numerous biotic and abiotic external noxious agents. Accordingly, the digestive tract is frequently involved in malfunctions within the organism. Together with the commensal intestinal flora, it regulates the immunological balance between inflammatory defense processes and immune tolerance. Pathological changes in this system often cause chronic inflammatory bowel diseases including Crohn's disease and ulcerative colitis. This review article highlights the complex interaction between commensal microorganisms, the intestinal microbiome, and the intestinal epithelium-localized local immune system. The main functions of the human intestinal microbiome include (i) protection against pathogenic microbial colonization, (ii) maintenance of the barrier function of the intestinal epithelium, (iii) degradation and absorption of nutrients and (iv) active regulation of the intestinal immunity. The local intestinal immune system consists primarily of macrophages, antigen-presenting cells, and natural killer cells. These cells regulate the commensal intestinal microbiome and are in turn regulated by signaling factors of the epithelial cells and the microbiome. Deregulated immune responses play an important role and can lead to both reduced activity of the commensal microbiome and pathologically increased activity of harmful microorganisms. These aspects of chronic inflammatory bowel disease have become the focus of attention in recent years. It is therefore important to consider the immunological-microbial context in both the diagnosis and treatment of inflammatory bowel diseases. A promising holistic approach would include the most comprehensive possible diagnosis of the immune and microbiome status of the patient, both at the time of diagnostics and during therapy.

Salmonella contamination in poultry products is a significant concern due to its potential to cause severe economic losses and public health problems. On the other side, coccidiosis is induced by Eimeria (E.) species. involves the destruction of host intestinal epithelial cells and subsequent invasion of pathogens, resulting in performance reduction and enhanced pathogen infection in poultry and economic losses for the poultry industry. A study was conducted to evaluate the impact of Eimeria infection and Salmonella typhimurium (ST) on growth performance, Salmonella colonization, and ceca microbiota in turkey poult. A total of 420 one-day-old male turkey poults were randomly allocated into six treatments, with five replicated cages for each treatment, over a 21-day experimental period. The study followed a 2 × 3 factorial design. Treatments consisted of NC, negative control without any challenge; T1, challenged with 8000 oocysts of E. meleagrimitis and E. adenoeides at d 8; T2, challenged with 16,000 oocysts of E. meleagrimitis and E. adenoeides at d 8; T3, challenged with nalidixic acid-resistant Salmonella typhimurium (ST) at d 0; T4, challenged with ST at d 0 and 8000 oocysts of E. meleagrimitis and E. adenoeides at d 8; T5, challenged with ST at d 0 and 16,000 oocysts of E. meleagrimitis and E. adenoeides at d 8. The Eimeria challenge groups significantly reduced the BW compared to the non-challenge group (P < 0.001). The challenged groups decreased FI during 9-14 days of age (P < 0.01). Salmonella typhimurium did not affect BW entire trial period (P > 0.05). Gut permeability (GP) increased in the challenge groups compared to the NC group (P < 0.001). Both ST and Eimeria significantly decreased superoxide dismutase (SOD) in the liver (P < 0.01). The challenge groups had lower villus height (VH) and higher crypt depth (CD) compared to the NC group, resulting in decreased VH:CD ratio in the duodenum and jejunum (P < 0.01). The groups T1, T2, and T4 had significantly higher fat deposition than the NC group (P < 0.05). The coinfected groups (T4 and T5) had higher salmonella colonization in the spleen compared to the ST-infected group (T3, P < 0.05). The ST challenge significantly decreased alpha diversity, including pielou evenness and Shannon entropy (P < 0.05). The Proteobacteria phylum and Enterobacteriaceae family significantly increased in T5 compared to the NC, T1, T2, and T3 (P < 0.05). In conclusion, Eimeria infection negatively impacted growth, gut health, intestine barrier integrity, and histology, while Salmonella had a milder effect on performance. Coinfection with Salmonella and Eimeria spp. led to changes in gut microbiota and increased liver Salmonella colonization and fat deposition in turkey poults.

Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.

The human intestinal tract plays a pivotal role in safeguarding the body against noxious substances and microbial pathogens by functioning as a barrier. This barrier function is achieved through the combined action of physical, chemical, microbial, and immune components. Tea (Camellia sinensis) is the most widely consumed beverage in the world, and it is consumed and appreciated in a multitude of regions across the globe. Tea can be classified into various categories, including green, white, yellow, oolong, black, and dark teas, based on the specific processing methods employed. In recent times, there has been a notable surge in scientific investigation into the various types of tea. The recent surge in research on tea can be attributed to the plethora of bioactive compounds it contains, including polyphenols, polysaccharides, pigments, and theanine. The processing of different teas affects the active ingredients to varying degrees, resulting in a range of chemical reactions and the formation of different types and quantities of ingredients. The bioactive compounds present in tea are of great importance for the maintenance of the integrity of the intestinal barrier, operating through a variety of mechanisms. This literature review synthesizes scientific studies on the impact of the primary bioactive compounds and different processing methods of tea on the intestinal barrier function. This review places particular emphasis on the exploration of the barrier repair and regulatory effects of these compounds, including the mitigation of damage to different barriers following intestinal diseases. Specifically, the active ingredients in tea can alleviate damage to physical barriers and chemical barriers by regulating barrier protein expression. At the same time, they can also maintain the stability of immune and biological barriers by regulating the expression of inflammatory factors and the metabolism of intestinal flora. This investigation can establish a strong theoretical foundation for the future development of innovative tea products.

There is a significant global demand for precise diagnosis and effective treatment of IgA nephropathy (IgAN), with innate immunity, particularly the complement system, exerting a profound influence on its pathogenesis. Additionally, the gut-kidney axis pathway is vital in the emergence and development of IgAN.

We conducted a comprehensive search in the Web of Science database, spanning from January 1, 2000 to December 18, 2023. The gathered literature underwent a visual examination through CiteSpace, VOSviewer, and Scimago Graphica to delve into authors, nations, organizations, key terms, and other pertinent elements.

Between 2000 and 2023, a total of 720 publications were identified, out of which 436 publications underwent screening for highly relevant literature analysis. The average annual number of articles focusing on IgAN, innate immunity, and the gut-kidney axis is approximately 31, with an upward trend observed. In terms of research impact encompassing publication count and authorship, the United States emerged as the leading contributor. Prominent keywords included "complement", "activation", "microbe", "gut-kidney axis", "C4d deposition", "alternative pathway" and "B cells" along with other prospective hot topics.

The correlation between IgAN and innate immunity is a focal point in current scientific research. Recent literature underscores the significance of the gut-kidney axis, where intestinal microorganisms and metabolites may influence IgAN. The complement system, a key component of innate immunity, also has a crucial function.Advancements in prevention, diagnosis, and treatment hinge on unraveling this intricate relationship.

Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats.

The objective of this study was to evaluate the effects of dietary addition of lactic acid and glutamine, and their interactions, on growth performance, nutrient digestibility, digestive enzyme activity, intestinal barrier functions, microflora, and expressions of intestinal development-related genes of weaning piglets. Ninety-six 24-day-old weaning piglets (Duroc × Landrace × Yorkshire, weaned at 21 ± 1 d and fed the basal diet for a 3 d adaptation period) with initial body weight of 7.24 ± 0.09 kg were randomly assigned to one of four dietary treatments with six replicates per treatment and four pigs per replicate in a 2 × 2 factorial treatment arrangements: (1) CON (a 2-period basal diet; control), (2) LS (supplemented with 2% lactic acid), (3) GS (supplemented with 1% glutamine), and (4) LGS (supplemented with 2% lactic acid and 1% glutamine). The study lasted for 28 d. On days 25-28, fresh fecal samples were collected to evaluate apparent total tract digestibility (ATTD) of nutrients. After 28 d, one weaning pig per pen was euthanized, and physiological samples obtained. Results showed that the supplementation of lactic acid improved the ADFI of the pigs (p < 0.05), while the pigs fed the glutamine diet had a greater ADFI and higher G/F (p < 0.05), and there were significant interactive effects between lactic acid and glutamine on the ADFI and G/F of the pigs (p < 0.05). The ATTD of CP and ash for pigs fed with lactic acid was significantly enhanced, and pigs fed the glutamine diet had greater ATTD of CP and ash (p < 0.05), while there were significant interactive effects between lactic acid and glutamine on the ATTD of CP and ash of the pigs (p < 0.05). Pigs fed with lactic acid exhibited greater activity of α-amylase and lipase (p < 0.05); moreover, the activity of lipase in the pigs showed a significant interactive effect between lactic acid and glutamine (p < 0.05). There was a greater villus height and villus height to crypt depth ratio in pigs fed with lactic acid (p < 0.05), and the villus height to crypt depth ratio of pigs fed with glutamine was greater (p < 0.05). There were greater GLUT2, IGF-1, TGF-β2, OCLN, and ZO-1 mRNA levels in pigs fed with lactic acid (p < 0.05), and the supplementation of glutamine increased SGLT1, GLUT2, PepT1, IGF-1, IGF-1R, TGFβ-2, GLP-2, and OCLN mRNA levels (p < 0.05), Additionally, expressions of SGLT1, GLUT2, PepT1, IGF-1, IGF-1R, TGFβ-2, GLP-2, CLDN-2, OCLN, and ZO-1 mRNA levels of pigs showed a positive interactive effect between lactic acid and glutamine (p < 0.05). Supplementation of lactic acid significantly increased the populations of Bifidobacterium in cecal digesta, Lactobacillus in colonic digesta, and the content of butyric acid in colonic digesta (p < 0.05). In addition, there were significant interactive effects between lactic acid and glutamine on populations of Bifidobacterium in cecal digesta, Lactobacillus in colonic digesta, and the content of acetic acid, butyric acid, and total VFAs in cecal digesta of the pigs (p < 0.05). Collectively, the current results indicate that dietary supplementation with lactic acid and glutamine had a positive synergistic effect on weaning pigs, which could improve growth performance through promoting the development of the small intestine, increasing digestive and barrier function, and regulating the balance of microflora in pigs, and which might be a potential feeding additive ensemble to enhance the health and growth of weaning piglets in the post-antibiotic era.

Early nutritional management approach greatly impacts broilers' performance and resistance against coccidiosis. The current study explored the impact of post-hatch feeding with a combination of glutamine (Glut) and different levels of omega-3 on broiler chickens' growth performance, muscle building, intestinal barrier, antioxidant ability and protection against avian coccidiosis. A total of six hundred Cobb 500 was divided into six groups: first group (fed basal diet and unchallenged (control) and challenged (negative control, NC) groups were fed a basal diet without additives, and the other groups were infected with Eimeria spp and supplemented with 1.5% Glut alone or with three different levels of omega-3 (0.25, 0.5 and 1%) during the starter period. Notable improvement in body weight gain was observed in the group which fed basal diet supplemented with glut and 1% omega 3 even after coccidia infection (increased by 25% compared challenged group) while feed conversion ratio was restored to control. Myogeneis was enhanced in the group supplemented with Glut and omega-3 (upregulation of myogenin, MyoD, mechanistic target of rapamycin kinase and insulin like growth factor-1 and downregulating of myostatin genes). Groups supplemented with Glut and higher levels of omega-3 highly expressed occluding, mucin-2, junctional Adhesion Molecule 2, b-defensin-1 and cathelicidins-2 genes. Group fed 1% Glut + omega-3 showed an increased total antioxidant capacity and glutathione peroxidase and super oxide dismutase enzymes activities with reduced levels of malondialdehyde, reactive oxygen species and H2O2. Post-infection, dietary Glut and 1% omega-3 increased intestinal interleukin-10 (IL) and secretory immunoglobulin-A and serum lysozyme, while decreased the elevated inflammatory mediators comprising interleukin IL-6, tumor necrosis factor-alpha, nitric oxide (NO) and inducible NO synthase. Fecal oocyst excretion and lesions score severity were lowered in the group fed 1% Glut and omega 3. Based on these findings, dietary Glut and omega-3 supplementation augmented restored overall broilers' performance after coccidial challenge.

One important feature of corn distillers dried grains with solubles (DDGS) is its high leucine:lysine ratio, which can inhibit chicken growth by causing branched-chain amino acid (BCAA) antagonism. The current study was conducted to investigate the effects of BCAA imbalance of inclusion of DDGS and whether additional dietary valine and isoleucine could alleviate the negative effects in broilers. A total of 640 0-d-old male Cobb 500 broilers were allocated into 4 treatments with 8 replicates and reared until d 42. The four different dietary groups were as follows: 1) control (CON) group (corn-soybean meal-based diet); 2) 30% DDGS (30D) group (replacing soybean meal with 30% DDGS); 3) 30D + additional valine and isoleucine (30DB) group; and 4) the group of 30DB + additional valine and isoleucine to provide the same leucine:valine and leucine:isoleucine ratios as the CON group (30DBB). The analyzed leucine:lysine ratios of the CON group were 1.36/1.41/1.46 (starter/grower/finisher phase), whereas the average leucine:lysine ratios of the 30% DDGS groups were 1.61/1.70/1.78 (starter/grower/finisher phase). The 30% DDGS groups (30D, 30DB, and 30DBB) negatively affected body weight (BW) from d 7 to 42 and BW gain (BWG), feed intake, carcass weight, breast muscle weight, and jejunal and ileal villus height:crypt depth during the overall period (d 0 to 42) (P < 0.05). Furthermore, the 30% DDGS groups significantly altered expression levels of jejunal tight junction proteins, breast muscle mechanistic target of rapamycin (mTOR) pathway-related genes, BCAA catabolism genes, and AA transporters compared to the CON (P < 0.01). The 30% DDGS groups showed differences in beta-diversity indices compared to the CON group (P < 0.05). The 30DBB group showing the lowest d 21 and 42 BW and overall BWG had the largest differences compared to the CON group in most measurements. In conclusion, excessive replacement of soybean meal with DDGS can significantly increase leucine levels, which may negatively affect chicken growth. Additionally, inappropriate ratios of valine and isoleucine can further decrease growth performance.

Jianpi huoxue decoction (JHD), a Chinese herbal formula, is commonly used for treating alcohol-associated liver disease (ALD). This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.

The Sprague-Dawley rats were randomly divided into three groups: control group, model group and JHD group. They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol (model group, n=10; JHD group, n=10) or isocaloric maltose dextrin (control group, n=10) for 6 weeks. After 3 weeks of feeding, the mice in the JHD group were given JHD (10 mL/kg/day) by gavage for 3 weeks, and those in the control and model groups received equal amounts of double-distilled water for the same period of time. Afterwards, all the rats were given lipopolysaccharide (LPS) by gavage and sacrificed 3.5 h later. LPS levels were measured in the portal blood to evaluate gut leakage. Transmission electron microscopy (TEM) was used to observe ultrastructural changes in the intestinal tract. Adherens junction (AJ) and tight junction (TJ) proteins were detected by Western blotting, immunofluorescence or immunohistochemistry.

JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis, inflammation and LPS expression. It improved pathological changes in the liver and alleviated intestinal ultrastructure injury. Moreover, it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens-1 (ZO-1) and occludin. It suppressed the activation of myosin light chain (MLC) phosphorylation.

JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.

Cordyceps polysaccharide (CSP) has been shown to exhibit anti-inflammatory and antioxidant effects, with potential applications in ischemic stroke. This work is to explore the interventional potential of CSP in MCAO rats and the effects on the intestinal and cerebral IL-23/IL-17 axis. We conducted pharmacological experiments and mechanism exploration in MCAO rats. Our research showed that CSP improved the neurological function and cerebral pathological morphology, reduced cerebral infarction volume and water content in MCAO rats. We also found that CSP significantly decreased the IL-1β, TNF-α and IL-6 in the ischemic brain and enhanced the ability of MCAO rats to resist oxidative stress. Additionally, CSP improved intestinal barrier, inhibited the activation of the TLR4/Myd88/NF-κβ signaling pathway and IL-23/IL-17 axis. The study results demonstrated the effectiveness of CSP in interfering with MCAO rats. The mechanism appears to be related to protecting the intestinal barrier and inhibiting the IL-23/IL-17 axis.

Background: Allergic Rhinitis (AR) is an atopic disease affecting the upper airways of predisposed subjects exposed to aeroallergens. This study evaluates the effects of a mix of specific probiotics (L. acidophilus PBS066, L. rhamnosus LRH020, B. breve BB077, and B. longum subsp. longum BLG240) on symptoms and fecal microbiota modulation in subjects with AR. Methods: Probiotic effects were evaluated at the beginning (T0), at four and eight weeks of treatment (T1 and T2, respectively), and after four weeks of follow-up from the end of treatment (T3) (n = 19) compared to the placebo group (n = 22). AR symptoms and quality of life were evaluated by the mini rhinitis quality of life questionnaire (MiniRQLQ) at each time point. Allergic immune response and fecal microbiota compositions were assessed at T0, T2, and T3. The study was registered on Clinical-Trial.gov (NCT05344352). Results: The probiotic group showed significant improvement in the MiniRQLQ score at T1, T2, and T3 vs. T0 (p < 0.01, p < 0.05, p < 0.01, respectively). At T2, the probiotic group showed an increase in Dorea, which can be negatively associated with allergic diseases, and Fusicatenibacter, an intestinal bacterial genus with anti-inflammatory properties (p-value FDR-corrected = 0.0074 and 0.013, respectively). Conversely, at T3 the placebo group showed an increase in Bacteroides and Ruminococcaceae unassigned, (p-value FDR-corrected = 0.033 and 0.023, respectively) which can be associated with allergies, while the probiotic group showed a significative increase in the Prevotella/Bacteroides ratio (p-value FDR-corrected = 0.023). Conclusions: This probiotic formulation improves symptoms and quality of life in subjects with AR, promoting a shift towards anti-inflammatory and anti-allergic bacterial species in the intestinal microbiota.

The effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding.

Renal fibrosis represents a critical pathological condition in the progression of renal dysfunction, characterized by aberrant accumulation of extracellular matrix (ECM) and structural alterations in renal tissue. Recent research has highlighted the potential significance of gut microbiota and demonstrated their influence on host health and disease mechanisms through the production of bioactive metabolites. This review examines the role of alterations in gut microbial composition and their metabolites in the pathophysiological processes underlying renal fibrosis. It delineates current therapeutic interventions aimed at modulating gut microbiota composition, encompassing dietary modifications, pharmacological approaches, and probiotic supplementation, while evaluating their efficacy in mitigating renal fibrosis. Through a comprehensive analysis of current research findings, this review enhances our understanding of the bidirectional interaction between gut microbiota and renal fibrosis, establishing a theoretical foundation for future research directions and potential clinical applications in this domain.

The gut-brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation and influencing numerous critical processes within the body. Over the past decade, research has increasingly focused on the GBA in the context of inflammatory bowel disease (IBD). Beyond its well-documented effects on the GBA-enteric nervous system and vagus nerve dysregulation, and gut microbiota misbalance-IBD also leads to impairments in the metabolic and cellular functions: metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton dysregulation. These systemic effects are currently underexplored in relation to the GBA; however, they are crucial for the nervous system cells' functioning. This review summarizes the studies on the particular mechanisms of metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton impairments in IBD. Understanding the involvement of these processes in the GBA may help find new therapeutic targets and develop systemic approaches to improve the quality of life in IBD patients.

This study investigated the best oral delivery strategy (gavage or feed) for the B. subtilis expressing the chicken anti-microbial peptide cNK-2 (B. subtilis-cNK-2) in comparison to monensin, in chickens challenged with Eimeria acervulina (E. acervulina). A total of 120 broiler chickens were randomly allocated into 5 treatment groups in a completely randomized design: 1) uninfected chickens fed with basal diet (NC), 2) E. acervulina-infected chickens fed a basal diet (PC), 3) E. acervulina-infected chickens fed a basal diet supplemented with 90 mg monensin/kg feed (MO), 4) E. acervulina-infected chickens fed a basal diet and orally gavaged with B. subtilis-cNK-2 at 1 × 1010 cfu/d (CNK-O), and 5) E. acervulina-infected chickens fed a basal diet mixed with B. subtilis-cNK-2 at 1 × 1010 cfu/kg feed (CNK-F). The challenge consisted of 5,000 sporulated E. acervulina oocysts through oral gavage on d 15. Body weights were measured on d 7, 14, 21, and 23. Duodenal tissue and digesta samples were collected at 6 d postinfection (dpi) to assess the gut integrity, oxidative stress, mucosal immunity, and the gut microbiome. Fecal samples were collected from 6 to 8 dpi to enumerate the oocyst shedding. Chickens in the CNK-O group showed improved (P < 0.05) growth performance, gut integrity, and mucosal immunity compared to PC, comparable to chickens in the MO group. Chickens in the MO, CNK-F, and CNK-O treatment groups all showed lower (P < 0.05) oocyst shedding compared to PC chickens. Moreover, distinct cytokine profile, oxidative stress measures, tight junction proteins, and shifts in the gut microbiome with associated functional changes were observed in all challenge groups. In conclusion, we showed that the oral administration of B. subtilis-cNK-2 improved growth performance, enhanced local protective immunity, and reduced fecal oocyst shedding in broiler chickens infected with E. acervulina, demonstrating potential use of B. subtilis-cNK-2 as an alternative to antibiotics to protect chickens against coccidiosis.

Chitosan nanoparticles (NPs) are well-recognized as promising vehicles for delivering anticancer drugs due to their distinctive characteristics. They have the potential to enclose hydrophobic anticancer molecules, thereby enhancing their solubilities, permeabilities, and bioavailabilities; without the use of surfactant, i.e., through surfactant-free solubilization. This allows for higher drug concentrations at the tumor sites, prevents excessive toxicity imparted by surfactants, and could circumvent drug resistance. Moreover, biomedical engineers and formulation scientists can also fabricate chitosan NPs to slowly release anticancer agents. This keeps the drugs at the tumor site longer, makes therapy more effective, and lowers the frequency of dosing. Notably, some types of cancer cells (fallopian tube, epithelial tumors of the ovary, and primary peritoneum; lung, kidney, ependymal brain, uterus, breast, colon, and malignant pleural mesothelioma) have overexpression of folate receptors (FRs) on their outer surface, which lets folate-drug conjugate-incorporated NPs to target and kill them more effectively. Strikingly, there is evidence suggesting that the excessively produced FR&αgr (isoforms of the FR) stays consistent throughout treatment in ovarian and endometrial cancer, indicating resistance to conventional treatment; and in this regard, folate-anchored chitosan NPs can overcome it and improve the therapeutic outcomes. Interestingly, overly expressed FRs are present only in certain tumor types, which makes them a promising biomarker for predicting the effectiveness of FR-targeted therapy. On the other hand, the folate-modified chitosan NPs can also enhance the oral absorption of medicines, especially anticancer drugs, and pave the way for effective and long-term low-dose oral metronomic scheduling of poorly soluble and permeable drugs. In this review, we talked briefly about the techniques used to create, characterize, and tailor chitosan-based NPs; and delved deeper into the potential applications of folate-engineered chitosan NPs in treating various cancer types.

An anti-inflammatory diet is characterised by incorporating foods with potential anti-inflammatory properties, including fruits, vegetables, whole grains, nuts, legumes, spices, herbs and plant-based protein. Concurrently, pro-inflammatory red and processed meat, refined carbohydrates and saturated fats are limited. This article explores the effects of an anti-inflammatory diet on non-communicable diseases (NCD), concentrating on the underlying mechanisms that connect systemic chronic inflammation, dietary choices and disease outcomes. Chronic inflammation is a pivotal contributor to the initiation and progression of NCD. This review provides an overview of the intricate pathways through which chronic inflammation influences the pathogenesis of conditions including obesity, type II diabetes mellitus, CVD, autoinflammatory diseases, cancer and cognitive disorders. Through a comprehensive synthesis of existing research, we aim to identify some bioactive compounds present in foods deemed anti-inflammatory, explore their capacity to modulate inflammatory pathways and, consequently, to prevent or manage NCD. The findings demonstrated herein contribute to an understanding of the interplay between nutrition, inflammation and chronic diseases, paving a way for future dietary recommendations and research regarding preventive or therapeutic strategies.

Intestinal permeabilization is central to the pathophysiology of chronic gut inflammation. This study investigated the efficacy of glucoraphanin (GR), prevalent in cruciferous vegetables, particularly broccoli, and its derivative sulforaphane (SF), in inhibiting tumor necrosis factor alpha (TNFα)-induced Caco-2 cell monolayers inflammation and permeabilization through the regulation of redox-sensitive events. TNFα binding to its receptor led to a rapid increase in oxidant production and subsequent elevation in the mRNA levels of NOX1, NOX4, and Duox2. GR and SF dose-dependently mitigated both these short- and long-term alterations in redox homeostasis. Downstream, GR and SF inhibited the activation of the redox-sensitive signaling cascades NF-κB (p65 and IKK) and MAPK ERK1/2, which contribute to inflammation and barrier permeabilization. GR (1 μM) and SF (0.5-1 μM) prevented TNFα-induced monolayer permeabilization and the associated reduction in the levels of the tight junction (TJ) proteins occludin and ZO-1. Both GR and SF also mitigated TNFα-induced increased mRNA levels of the myosin light chain kinase, which promotes TJ opening. Molecular docking suggests that although GR is mostly not absorbed, it could interact with extracellular and membrane sites in NOX1. Inhibition of NOX1 activity by GR would mitigate TNFα receptor downstream signaling and associated events. These findings support the concept that not only SF, but also GR, could exert systemic health benefits by protecting the intestinal barrier against inflammation-induced permeabilization, in part by regulating redox-sensitive pathways. GR has heretofore not been viewed as a biologically active molecule, but rather, the benign precursor of highly active SF. The consumption of GR and/or SF-rich vegetables or supplements in the diet may offer a means to mitigate the detrimental consequences of intestinal permeabilization, not only in disease states but also in conditions characterized by chronic inflammation of dietary and lifestyle origin.

Diacylglycerol O-acyltransferase 1 (DGAT1) is a key enzyme for fat absorption step in the enterocytes. We previously reported that DGAT1 inhibition increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in corn oil-loaded rats via protein kinase C (PKC) activation. In the present study, we investigated the mechanism with respect to the morphology and permeability of the small intestine, focusing on PKC function, and found that shortening of the intestinal villi and a decrease in the number of tdT-mediated dUTP-biotin nick-end labeling-positive cells in the tips of the villi were observed in the jejunum of DGAT1 inhibitor-treated rats loaded with corn oil. These results suggested that the tips of the villi were shed into the intestinal lumen. Next, fluorescein isothiocyanate-dextran, 110 kDa (FD-110) was administered intraduodenally to DGAT1 inhibitor-treated rats loaded with corn oil and we found that plasma FD-110 concentrations increased, indicating that the intestinal permeability to molecules with a molecular weight of approximately 110,000 (e.g., ALT and AST) increased. Taken together, the present results suggested that DGAT1 inhibitor-treatment in combination with corn oil causes ALT and AST to leak from the enterocytes into the blood by shedding the tips of the intestinal villi and increasing intestinal permeability.

Lactoferrin is an antimicrobial peptide (AMP) playing a pivotal role in numerous biological processes. The primary antimicrobial efficacy of lactoferrin is associated with its N-terminal end, which contains various peptides, such as lactoferricin and lactoferrampin. In this context, our research team has developed a refined chimeric 42-mer peptide known as cLF36 over the past few years. This peptide encompasses the complete amino acid sequence of camel lactoferrampin and partial amino acid sequence of lactoferricin. The peptide's activity against human, avian, and plant bacterial pathogens has been assessed using different biological platforms, including prokaryotic (P170 and pET) and eukaryotic (HEK293) expression systems. The peptide positively influenced the growth performance and intestinal morphology of chickens challenged with pathogen bacteria. Computational methods and in vitro studies showed the peptide's antiviral effects against hepatitis C virus, influenza virus, and rotavirus. The chimeric peptide exhibited higher activity against certain tumor cell lines compared to normal cells, which may be attributed to the peptide's interaction with negatively charged glycosaminoglycans on the surface of tumor cells. Importantly, this peptide exhibited no toxicity against host cells and demonstrated remarkable thermal and protease stability in serum. In conclusion, while our investigations suggest that the chimeric peptide, cLF36, may offer potential as a candidate or complementary option to some available antibiotics, antiviral agents, and chemical pesticides, significant uncertainties remain regarding its cost-effectiveness, as well as its pharmacodynamic and pharmacokinetic characteristics, which require further elucidation.

Parkinson's disease (PD) is a neurodegenerative disease affecting dopaminergic neurons in the nigrostriatal and gastrointestinal tracts, causing both motor and non-motor symptoms. This study examined the neuroprotective effects of trehalose. This sugar is confined in the gut due to the absence of transporters, so we hypothesized that trehalose might exert neuroprotective effects on PD through its action on the gut microbiota. We used a transgenic mouse model of PD (PrP-A53T G2-3) overexpressing human α-synuclein and developing GI dysfunctions. Mice were given water with trehalose, maltose, or sucrose (2% w/v) for 6.5 m. Trehalose administration prevented a reduction in tyrosine hydroxylase immunoreactivity in the substantia nigra (-25%), striatum (-38%), and gut (-18%) in PrP-A53T mice. It also modulated the gut microbiota, reducing the loss of diversity seen in PrP-A53T mice and promoting bacteria negatively correlated with PD in patients. Additionally, trehalose treatment increased the intestinal secretion of glucagon-like peptide 1 (GLP-1) by 29%. Maltose and sucrose, which break down into glucose, did not show neuroprotective effects, suggesting glucose is not involved in trehalose-mediated neuroprotection. Since trehalose is unlikely to cross the intestinal barrier at the given dose, the results suggest its effects are mediated indirectly through the gut microbiota and GLP-1.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

Diet is of major importance in modulating intestinal inflammation, as the gastrointestinal tract is directly exposed to high concentrations of dietary components. Procyanidins are flavan-3-ol oligomers abundant in fruits and vegetables. Although with limited or no intestinal absorption, they can have GI health benefits which can promote overall health. We previously observed that epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) dimers inhibit in vitro colorectal cancer cell proliferation and invasiveness. Inflammation-mediated intestinal barrier permeabilization can result in a chronic inflammatory condition and promote colorectal cancer onset/progression. Thus, this study investigated the structure-dependent capacity of ECG, EGCG and (-)-epicatechin (EC) dimers to inhibit tumor necrosis factor alpha (TNFα)-induced inflammation, oxidative stress, and loss of barrier integrity in Caco-2 cells differentiated into an intestinal epithelial cell monolayer. Cells were incubated with TNFα (10 ng/ml), in the absence/presence of ECG, EGCG and EC dimers. The three dimers inhibited TNFα-mediated Caco-2 cell monolayer permeabilization, modulating events involved in the loss of barrier function and inflammation, i.e. decreased tight junction protein levels; increased matrix metalloproteinases expression and activity; increased NADPH oxidase expression and oxidant production; activation of the NF-κB and ERK1/2 pathways and downstream events leading to tight junction opening. For some of these mechanisms, the galloylated ECG and EGCG dimers had stronger protective potency than the non-galloylated EC dimer. These differences could be due to differential membrane interactions as pointed out by molecular dynamics simulation of procyanidin dimers-cell membrane interactions and/or by differential interactions with NOX1. Results show that dimeric procyanidins, although poorly absorbed, can promote health by alleviating intestinal inflammation, oxidative stress and barrier permeabilization.

To investigate the quality of different ozone-oxidized surimi gels and their in vitro digestion and absorption characteristics, surimi rinsed with different concentrations of ozonated water (0, 8, 26 mg/L) were prepared. Then, the degree of oxidation and gel structure of surimi were determined, the in vitro digestion and absorption of the gels were simulated, and the digestion and absorption products were analyzed by LC-MS/MS. The results showed that the quality of surimi gels was improved after proper ozone oxidation. After ozone water rinsing, the dry matter digestibility, peptide, and amino acid content increased, and the changes of all three were in line with the Logistic kinetic model (R2 = 0.95-0.99). Caco-2 cell absorption experiments showed that the absorption rate of peptides and amino acids decreased after ozone water rinsing. In summary, ozone oxidation can promote the digestion of surimi gels, but it also reduces the absorption of peptides and amino acids by Caco-2 cells. This study provides a reference for the application of ozone in the food field.

Bifidobacterium bifidum strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α-induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α-induced increase in intestinal TJ permeability by interfering with TNF-α-induced enterocyte NF-κB p50/p65 and myosin light chain kinase (MLCK) gene activation. The BB1 protective effect against the TNF-α-induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α-induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, MLCK gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α-induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α-induced increase in intestinal epithelial TJ permeability via a PPAR-γ-dependent inhibition of NF-κB p50/p65 and MLCK gene activation.

Vitamin D3 (25-hydroxyvitamin D3 (VD)) and vitamin E (VE) have proven to have immunomodulatory and antioxidant functions along with capacities to improve the reproductive function in chickens. Coccidiosis in laying hens at different stages of growth has been shown to negatively affect performance, immune response, and oxidative status, thus increasing the cost of production. A study was conducted to evaluate the influence of dietary VD or VE on performance, gut health, immune response, and oxidative status of laying hens at peak production. Laying hens (23 wk-of-age, n = 225) were randomly allocated into 5 treatment groups (n = 9 hens/replicate) with 5 replicate groups each: 1) unchallenged control (UC), 2) pair-fed control (PF), 3) challenged control (CC), 4) challenged control top-dressed with 5,000 IU of 25-hydroxyvitamin D3 (VD) per kg of diet, and 5) challenged control top-dressed with 100 IU of DL-α-tocopherol (VE). At 25 wk-of-age, hens grouped in CC, VD, and VE were challenged with mixed Eimeria spp. to induce coccidiosis. VD or VE supplemented hens did not impact bird body weight; however, egg production increased by 10.36% and 13.77%, respectively (P < 0.0001). Furthermore, the gut health of the hens was improved with either VD or VE supplementation, as indicated by lowered gut permeability and intestinal lesion scores (P < 0.05). VE significantly reduced the heterophil count (P = 0.0490) alongside numerically increasing the peripheral CD4+ and CD8+ T cells and monocyte counts (P > 0.05). Both VD or VE increased the TAC at 14 DPI compared to UC (P<0.05). Preliminary findings suggest that dietary VD or VE supplementation has the potential to improve gut health, modulate the immune response, and increase egg production in coccidiosis-infected laying hens.

High-fat diet (HFD) feeding is known to cause intestinal barrier disruption, thereby triggering severe intestinal inflammatory disease. Indole-3-aldehyde (IAld) has emerged as a potential candidate for mitigating inflammatory responses and maintaining intestinal homeostasis. However, the role of IAld in the HFD-related intestinal disruption remains unclear. In this study, 48 7 week-old male C57BL/6J mice were assigned to four groups: the normal chow diet (NCD) group received a NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented with 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented with 600 mg/kg IAld in the HFD. The results showed that dietary IAld supplementation ameliorated fat accumulation and metabolic disorders, which are associated with reduced intestinal permeability. This reduction potentially led to decreased systemic inflammation and enhanced intestinal barrier function in HFD-fed mice. Furthermore, we found that IAld promoted intestinal stem cell (ISC) proliferation by activating aryl hydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest that IAld restores the HFD-induced intestinal barrier disruption by promoting AHR-mediated ISC proliferation.