IgA-producing Cells Research Articles

Coated oregano essential oil and cinnamaldehyde compounds supplementation improves growth performance, enhances immune responses, and inhibits cecal Escherichia coli proliferation of broilers.

Plant essential oils are unstable due to high volatility and easy oxidation, while microencapsulation provides a potentially effective strategy for increasing the stability of natural essential oils and preserving their function. This study examined the effects of feeding coated oregano essential oil and cinnamaldehyde (COEC) compounds on growth, immune organ development, intestinal morphology, mucosal immune function, and the cecal microbiota populations of broilers. Three hundred one-day-old male Arbor Acres broiler chicks were organized into 5 groups: 1) negative control fed basal diet alone (NC), 2) positive control receiving basal diet plus 50mg/kg of chlortetracycline (CTC), 3) basal diet plus 150mg/kg COEC (COEC150), 4) plus 300mg/kg COEC (COEC300), and 5) plus 450mg/kg COEC (COEC450). The supplement trial was continued for 42 d. The results showed that CTC, COEC300, and COEC450 treatments decreased the feed conversion ratio of broilers both in the starter and whole experiment phases, increased the height of jejunal villi at 21 d and the number of goblet cells and IgA-producing cells at 21 or 42 d compared with NC group (P < 0.05). Members of the COEC300 treatment group had a higher thymus weight index and jejunum length index than birds of NC or CTC groups at 21 d (P < 0.05). CTC and all COEC treatments decreased malondialdehyde content in jejunal mucosa at 42 d (P < 0.05). The population of Escherichia coli (E. coli) in the cecal digesta at 21 d was lower in the CTC, COEC300, and COEC450 treatment groups compared with the NC group (P < 0.05). In contrast to the CTC group, COEC supplementation dose-dependently accelerated body weight gain, improved jejunal morphology, decreased malondialdehyde content in jejunal mucosa, increased numbers of jejunal goblet cells and IgA-producing cells, and decreased the E. coli population in cecal digesta at 21 or 42 d (P < 0.05). Thus, we concluded that feeding broiler chickens with 300 or 450mg/kg in antibiotic-free diets can improve growth performance, enhance immune responses, and inhibit the proliferation of cecal pathogenic bacteria.

Medium- and Long-Term Immune Responses in the Small Intestine in Piglets from Oral Vaccination against Escherichia coli.

Post-weaning stress, together with Escherichia coli, are two of the key factors in the occurrence of post-weaning diarrhea. There are different commercial vaccines that induce immunity at the local or systemic level, improving farm health and avoiding economic losses in the pork industry. That is why the objective of this study was to evaluate the effect of an oral enterotoxigenic E. coli F4/F18 vaccine on immunity and intestinal integrity in the middle and long term after inoculation. The gene expression of the biomarkers indicative of cellular infiltration (calprotectin, CAL), tight junction proteins (occludin, OCL; zonulin, ZON; and claudin, CLA) and a panel of proinflammatory (interleukins, IL: IL1α, IL1β, IL6, IL8, IL12p35 and IL12p40; interferons, IFN: IFNα and IFNγ; and tumoral necrosis factor, TNF: TNFα) and anti-inflammatory mediator cytokines (TGFβ and IL10) were analyzed, as well as histomorphology in jejunum and ileum, the cell density of goblet cells, intraepithelial lymphocytes and IgA-producing cells. Differences were observed in ZON, CLA and CAL, with greater gene expression in observed in vaccinated piglets at 42 days post vaccination (dpv) in the ileum. Regarding the expression of cytokines, the vaccinated animals showed significant differences in IL1α, IL6, IL12p35, IL12p40, IFNα, IFNγ, TNFα and TGFβ at 42 dpv in the jejunum or ileum. The villi showed greater height in the vaccinated piglets and the ratio between villus height and crypt depth was significantly greater in the vaccinated group in the jejunum at 84 dpv. The count of IgA-producing cells shows higher values for the unvaccinated group in the ileum, while intraepithelial lymphocytes show a significant increase in both jejunum and ileum in vaccinated piglets. We can conclude that oral vaccination against E. coli produces an evident effect, which manifests itself even in the middle and long term after the challenge, including immune response, decrease in antimicrobials usage, better histological structure in intestine and the improvement of performance.

Effective reduction of pathogenic Escherichia coli and long-term immunity in pigs through early parenteral vaccination

ABSTRACT The present study aimed to examine the ability of a parenteral vaccine of direct application in suckling pigs to generate adaptive immunity against pathogenic Escherichia coli under field conditions as well as the long-term immune response at the end of productive life and the influence on the prevalence of pathogens involved in the Porcine Enteric Disease Complex (PEDC). Pigs were divided into vaccinated (n = 1,893) and non-vaccinated (control, n = 1,869) groups. We collected fecal swabs from nursery pigs presenting diarrhea and intestinal tissue at slaughter to assess E. coli virulence factors genes, PEDC pathogens, histology, IgA-producing cells, and cytokines levels. Fecal swabs: vaccinated group 0% pathogenic E. coli vs. 94.1% in control (p < 0.0001). Intestinal samples: Vaccinated group 35% positivity for E. coli vs. 85% in control (p = 0.001). PEDC pathogens: Only Lawsonia intracellularis was identified (40% of ileum and 20% of colon samples in vaccinated vs. 100% of ileum and 70% of colon in the control). Vaccinated had more intestine cellular infiltrate (p < 0.028), IgA-producing cells (p < 0.01), and inflammatory cytokines. The parenteral vaccine against E. coli for suckling pigs may be a strategy to control E. coli infection throughout pigs’ lives and our results suggest a possible interaction with L. intracellularis.

Pathogenic Immunoglobulin A-Producing Cells in Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and it remains a leading cause of kidney failure. Clinical manifestations of IgA are exacerbated by infections, and emerging data suggest that aberrant mucosal immune responses are important contributors to the immunopathogenesis of this disease. However, the exact stimuli, location and mechanism of nephritis-inducing IgA production remains unclear. In this focused review we explore recent developments in our understanding of the contribution of the mucosal immune system and mucosal-derived IgA-producing cells to the development of IgAN.

Comparison and characterization of the bacterial microbiota and SIgA production in different gastrointestinal segments in horses

In the gastrointestinal mucosa, there is a close cooperation between secretory immunoglobulin A (SIgA) and the composition of the microbiota, which aims to maintain homeostasis as well as act as a protective barrier. The purpose of this study was to determine the composition of microbiota and SIgA production in different parts of the digestive tract (small intestine, cecum, colon and rectum) of nine healthy horses and its reflection in the feces. For this purpose, we determined: the composition of the microbiome (by next-generation Sequencing of Hypervariable Regions V3-V4 and V7-V9 of the 16 S rRNA gene analysis), the amount of SIgA in the intestinal content samples (by ELISA), as well as the number of IgA-producing cells (IgA+) in the tissue samples (by immohistochemical analysis). Significant differences were observed between the small intestine and the large colon in the composition and diversity of the microbiome, as well as the number of IgA + cells in the mucosal lamina propria and the abundance of SIgA in the intestinal lumen. The small intestine in relation to the large colon is characterised by fewer IgA + cells, more SIgA in the intestinal contents and a less diverse microbiome. However, the cecum appears to be the third separate ecosystem, with a high number of IgA + cells and a diverse microbiome. The fecal sample reflects the current state of the large colon, both in terms of the microbiome and SIgA content; however, it is not known to what extent it may be influenced by dysbiosis in other parts of the digestive tract.

BTB and CNC homology 1 deficiency disrupts intestinal IgA secretion through regulation of polymeric immunoglobulin receptor expression.

Immunoglobulin A (IgA)-mediated mucosal immunity is important for the host because it contributes to reducing infection risk and to establishing host-microbe symbiosis. BTB and CNC homology 1 (Bach1) is a transcriptional repressor with physiological and pathophysiological functions that are of particular interest for their relation to gastrointestinal diseases. However, Bach1 effects on IgA-mediated mucosal immunity remain unknown. For this study using Bach1-deficient (Bach1-/-) mice, we investigated the function of Bach1 in IgA-mediated mucosal immunity. Intestinal mucosa, feces, and plasma IgA were examined using immunosorbent assay. After cell suspensions were prepared from Peyer's patches and colonic lamina propria, they were examined using flow cytometry. The expression level of polymeric immunoglobulin receptor (pIgR), which plays an important role in the transepithelial transport of IgA, was evaluated using Western blotting, quantitative real-time PCR, and immunohistochemistry. Although no changes in the proportions of IgA-producing cells were observed, the amounts of IgA in the intestinal mucosa were increased in Bach1-/- mice. Furthermore, plasma IgA was increased in Bach1-/- mice, but fecal IgA was decreased, indicating that Bach1-/- mice have abnormal secretion of IgA into the intestinal lumen. In fact, Bach1 deficiency reduced pIgR expression in colonic mucosa at both the protein and mRNA levels. In the human intestinal epithelial cell line LS174T, suppression of Bach1 reduced pIgR mRNA stability. In contrast, overexpression of Bach1 increased pIgR mRNA stability. These results demonstrate that Bach1 deficiency causes abnormal secretion of IgA into the intestinal lumen via suppression of pIgR expression.

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3–10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.

Lrba participates in the differentiation of IgA+ B lymphocytes through TGFβR signaling.

Lrba is a cytoplasmic protein involved in vesicular trafficking. Lrba-deficient (Lrba-/-) mice exhibit substantially higher levels of IgA in both serum and feces than wild-type (WT) mice. Transforming growth factor β1 (TGFβ1) and its receptors (TGFβR I and II) is essential for differentiating IgA+ B cells. Furthermore, increased IgA production suggests a potential connection between Lrba and the TGFβR signaling pathway in IgA production. However, the specific function of Lrba in B cell biology remains unknown. Given the increased IgA levels in Lrba-/- mice, the goal in this work was to explore the lymph organs where the switch to IgA occurs, and if TGFβR function is affected. Non-immunized Lrba-/- mice were compared with Lrba+/+ mice. IgA levels in the serum and feces, as well as during peripheral B cell development, were determined. IgA+ B cells and plasma cells were assessed in the small intestine and secondary lymphoid organs, such as the spleen, mesenteric lymph nodes, and Peyer's patches. The TGFβR signaling pathway was evaluated by determining the expression of TGFβR on B cells. Additionally, SMAD2 phosphorylation was measured under basal conditions and in response to recombinant TGFβ. Finally, confocal microscopy was performed to investigate a possible interaction between Lrba and TGFβR in B cells. Lrba-/- mice exhibited significantly higher levels of circulating IgA, IgA+ B, and plasma cells than in peripheral lymphoid organs those in WT mice. TGFβR expression on the membrane of B cells was similar in both Lrba-/- and Lrba+/+ mice. However, intracellular TGFβR expression was reduced in Lrba-/- mice. SMAD2 phosphorylation showed increased levels under basal conditions; stimulation with recombinant TGFβ elicited a poorer response than in that in Lrba+/+ B cells. Finally, we found that Lrba colocalizes with TGFβR in B cells. Lrba is essential in controlling TGFβR signaling, subsequently regulating SMAD2 phosphorylation on B cells. This mechanism may explain the increased differentiation of IgA+ B cells and production of IgA-producing plasma cells.

Development of Orally Ingestible IgA Antibody Drugs to Maintain Symbiosis Between Humans and Microorganisms.

In recent years, dysbiosis, abnormalities in the gut microbiota, has been reported to be associated with the development of many diseases, and improving the gut microbiota is important for health maintenance. It has been shown that the host recognizes and regulates intestinal bacteria by means of IgA antibodies secreted into the gut, but the precise nature of the commensal gut bacteria recognized by each IgA antibody is unclear. We have cloned monoclonal IgA antibodies from mouse intestinal IgA-producing cells and are searching for bacterial molecules recognized by each IgA clone. Although the interaction of IgA antibodies with intestinal bacteria is still largely unknown and requires further basic research, we discuss the potential use of orally ingestible IgA antibodies as agents to improve intestinal microbiota.

Advances in the treatment of IgA nephropathy with biological agents.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease, and the "four-hit" theory represents its currently accepted pathogenic mechanism. Mucosal immunity triggered by infections in the respiratory tract, intestines, or other areas leads to antigen presentation, T cell stimulation, B cell maturation, and the production of IgA-producing plasma cells. The proteins B-lymphocyte stimulator (BLyS) and aproliferation-inducing ligand (APRIL) are involved in this process, and alternative complement and lectin pathway activation are also part of the pathogenic mechanism. Kidney DiseaseImproving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking, with renin-angiotensin-aldosterone system inhibitors being the primary therapy. Recent research shows that biological agents can significantly reduce proteinuria, stabilize the estimated glomerular filtration rate, and reverse some pathological changes, such as endocapillary proliferation and crescent formation. There are four main categories of biological agents used to treat IgA nephropathy, specifically anti-CD20 monoclonal antibodies, anti-BLyS or APRIL monoclonal antibodies, monoclonal antibodies targeting both BLyS and APRIL (telitacicept and atacicept), and monoclonal antibodies inhibiting complement system activation (narsoplimab and eculizumab). However, further research on the dosages, treatment duration, long-term efficacy, and safety of these biological agents is required.

Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice

Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.

TGF-β1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM+ B cells apoptosis via Bax/Bcl2-Caspase3 pathway.

Transforming growth factor β1 (TGF-β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-β1 expression via activating Tregs. Besides, recombinant porcine TGF-β1 decreased the percentage of CD21+ B cells within the lymphocyte population in vitro. We further found that TGF-β1 reduced the IgA-secreting B cell numbers and also inhibited plasma cell differentiation. Additional investigations revealed that TGF-β1 induced the apoptosis of IgM+ B cells in both peyer's patches (PPs) and peripheral blood (PB) through the activation of the Bax/Bcl2-Caspase3 pathway. Conversely, the application of the TGF-β1 signaling inhibitor SB431542 significantly antagonized the TGF-β1-induced reduction of IgA secretion and B cell apoptosis and restored plasma cell differentiation. Collectively, TGF-β1 plays an important role in regulating the survival and differentiation of porcine IgA-secreting B cells through the classical mitochondrial apoptosis pathway. These findings will facilitate future mucosal vaccine designs that target the regulation of TGF-β1 for the control of enteric pathogens in the pig industry.

Gut bacteria induce IgA expression in pituitary hormone-secreting cells during aging

Pituitary hormone decline is a hallmark of aging. However, the precise gene regulation mechanism during pituitary aging is unclear. Here, we characterized the cell population alteration and global transcriptional change during pituitary aging through single-cell RNA sequencing (scRNA-seq). We found that mRNA-encoding components of protein translational machinery declined the most in the pituitary during aging. Remarkably, Immunoglobulin A (IgA) was found to be expressed in hormone-secreting cells, and the IgA expression level increased dramatically in aged pituitary. Moreover, the pituitary IgA expression was regulated by gut microbiota. The non-hematopoietic origin of the IgA+ cells in the pituitary was further confirmed through bone marrow transplantation. Somatotropes were identified as the most prominent IgA-producing cells through lineage tracing. Thus, pituitary hormone-secreting cells can generate IgA in an age-dependent manner, and such a process is influenced by gut bacteria.

Fasting-mimicking diet drives antitumor immunity against colorectal cancer by reducing IgA-producing cells.

As a safe, feasible, and inexpensive dietary intervention, fasting-mimicking diet (FMD) exhibits excellent antitumor efficacy by regulating metabolism and boosting antitumor immunity. A better understanding of the specific mechanisms underlying the immunoregulatory functions of FMD could help improve and expand the clinical application of FMD-mediated immunotherapeutic strategies. In this study, we aimed to elucidate the role of metabolic reprogramming induced by FMD in activation of antitumor immunity against colorectal cancer (CRC). Single-cell RNA sequencing (scRNA-seq) analysis of intratumoral immune cells revealed that tumor-infiltrating IgA+ B cells were significantly reduced by FMD treatment, leading to the activation of antitumor immunity and tumor regression in murine CRC models. Mechanistically, FMD delayed tumor growth by repressing B cell class switching to IgA. Therefore, FMD-induced reduction of IgA+ B cells overcame the suppression of CD8+ T cells. The immunoregulatory and antitumor effects of FMD intervention were reversed by IgA+ B cell transfer. Moreover, FMD boosted fatty acid oxidation (FAO) to trigger RUNX3 acetylation, thus inactivating Cα gene transcription and IgA class switching. IgA+ B cell expansion was also impeded in patients placed on FMD, while B cell expression of CPT1A, the rate-limiting enzyme of FAO, was increased. Furthermore, CPT1A expression was negatively correlated with both IgA+ B cells and IgA secretion within CRC. Together, these results highlight that FMD holds great promise for treating CRC. Furthermore, the degree of IgA+ B cell infiltration and FAO-associated metabolic status are potential biomarkers for evaluating FMD efficacy.

Elevated levels of enteric IgA in an unimmunised mouse model of Hyper IgM syndrome derived from gut-associated secondary lymph organs even in the absence of germinal centres.

Patients with Human Hyper IgM syndromes (HIGM) developed pulmonary and gastrointestinal infections since infancy and most patients have mutations in the CD40 ligand (CD40L) gene. Most HIGM patients compared to healthy subjects have higher/similar IgM and lower IgG, and IgA serum concentrations but gut antibody concentrations are unknown. CD40L on activated T-cells interacts with CD40 on B-cells, essential for the formation of germinal centres (GCs) inside secondary lymphoid organs (SLOs), where high-affinity antibodies, long-lived antibody-secreting plasma cells, and memory B-cells, are produced. C57BL6-CD40 ligand deficient mice (C57BL6-cd40l -/-), are a model of HIGM, because serum immunoglobulin concentrations parallel levels observed in HIGM patients and have higher faecal IgA concentrations. In mice, TGFβ and other cytokines induce IgA production. To compare and evaluate B-cell populations and IgA-producing plasma cells in peritoneal lavage, non-gut-associated SLOs, spleen/inguinal lymph nodes (ILN), and gut-associated SLOs, mesenteric lymph nodes (MLN)/Peyer´s patches (PP) of unimmunised C57BL6-cd40l -/- and C57BL6-wild-type (WT)mice. Peritoneal lavages, spleens, ILN, MLN, and PP from 8-10 weeks old C57BL6-cd40l -/- and WT mice, were obtained. Organ cryosections were analysed by immunofluorescence and B-cell populations and IgA-positive plasma cell suspensions by flow cytometry. In unimmunised WT mice, GCs were only observed in the gut-associated SLOs, but GCs were absent in all C57BL6-cd40l -/- SLOs. PP and MLN of C57BL6-cd40l -/- mice exhibited a significantly higher number of IgA-producing cells than WT mice. In the spleen and ILN of C57BL6-cd40l- /- mice IgA-producing cells significantly decreased, while IgM-positive plasma cells increased. C57BL6-cd40l -/- B-1 cells were more abundant in all analysed SLOs, whereas in WT mice most B-1 cells were contained within the peritoneal cavity. C57BL6-cd40l -/- B-cells in MLN expressed a higher TGFβ receptor-1 than WT mice. Mouse strains small intestine microvilli (MV), have a similar frequency of IgA-positive cells. Together our results confirm the role of PP and MLN as gut inductive sites, whose characteristic features are to initiate an IgA preferential immune response production in these anatomical sites even in the absence of GCs. IgA antibodies play a pivotal role in neutralising, eliminating, and regulating potential pathogens and microorganisms in the gut.

IgA-producing B cells in lung homeostasis and disease.

Immunoglobulin A (IgA) is the most abundant Ig in mucosae where it plays key roles in host defense against pathogens and in mucosal immunoregulation. Whereas intense research has established the different roles of secretory IgA in the gut, its function has been much less studied in the lung. This review will first summarize the state-of-the-art knowledge on the distribution and phenotype of IgA+ B cells in the human lung in both homeostasis and disease. Second, it will analyze the studies looking at cellular and molecular mechanisms of homing and priming of IgA+ B cells in the lung, notably following immunization. Lastly, published data on observations related to IgA and IgA+ B cells in lung and airway disease such as asthma, cystic fibrosis, idiopathic pulmonary fibrosis, or chronic rhinosinusitis, will be discussed. Collectively it provides the state-of-the-art of our current understanding of the biology of IgA-producing cells in the airways and identifies gaps that future research should address in order to improve mucosal protection against lung infections and chronic inflammatory diseases.

Fructose malabsorption in ChREBP-deficient mice disrupts the small intestine immune microenvironment and leads to diarrhea-dominant bowel habit changes.

The mechanism by which incompletely absorbed fructose causes gastrointestinal symptoms is not fully understood. In this study, we investigated the immunological mechanisms of bowel habit changes associated with fructose malabsorption by examining Chrebp-knockout mice exhibiting defective fructose absorption. Mice were fed a high-fructose diet (HFrD), and stool parameters were monitored. The gene expression in the small intestine was analyzed by RNA sequencing. Intestinal immune responses were assessed. The microbiota composition was determined by 16S rRNA profiling. Antibiotics were used to assess the relevance of microbes for HFrD-induced bowel habit changes. Chrebp-knockout (KO) mice fed HFrD showed diarrhea. Small-intestine samples from HFrD-fed Chrebp-KO mice revealed differentially expressed genes involved in the immune pathways, including IgA production. The number of IgA-producing cells in the small intestine decreased in HFrD-fed Chrebp-KO mice. These mice showed signs of increased intestinal permeability. Chrebp-KO mice fed a control diet showed intestinal bacterial imbalance, which the HFrD exaggerated. Bacterial reduction improved diarrhea-associated stool parameters and restored the decreased IgA synthesis induced in HFrD-fed Chrebp-KO mice. The collective data indicate that gut microbiome imbalance and disrupting homeostatic intestinal immune responses account for the development of gastrointestinal symptoms induced by fructose malabsorption.

Coprococcus eutactus, a Potent Probiotic, Alleviates Colitis via Acetate-Mediated IgA Response and Microbiota Restoration.

Inflammatory bowel disease (IBD) is a complex disease characterized by relapsing episodes of inflammation of the colonic mucosa. Research into IBD suggests that this disease condition is caused by alterations in resident mucosal bacterial populations. Our previous study showed that Coprococcus was significantly elevated during the improvement of IBD. Human metagenome database GMrepo also indicates Coprococcus, in particular, Coprococcus eutactus (C. eutactus), which was negatively associated with IBD. The current study implied the alleviated effects and mechanisms of C. eutactus on dextran sodium sulfate-induced experimental colitis mice. Gavage with C. eutactus-ameliorated acute colitis, as evidenced, relieved weight loss, decreased concentrations of proinflammatory cytokines TNF-α, IL-1β, and IL-6, and increased anti-inflammatory factors, IL-4, IL-5, and IL-10. In addition, C. eutactus enhanced the maturation of goblet cells and the expressions of mucins and restored the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1. As a short-chain fatty acid-producing bacterium, C. eutactus mainly generates acetic acid. Interestingly, not only high levels of secretory immunoglobulin A (SIgA) but also increased IgA-producing plasma cells were observed in colitis mice during the administration of C. eutactus. Importantly, our data demonstrated that colonic SIgA is specifically coated on pathogens of Enterobacteriaceae. Owing to the selective binding effect of SIgA on microorganisms, the microbial diversity in the intestinal lumen and mucosa of C. eutactus-treated colitis mice was significantly restored, and the microbiota structure was remodeled. These findings provide substantial insight that C. eutactus as a promising probiotic can ameliorate colitis. In conclusion, our findings may deliver a novel approach to the prevention and biotherapy of IBD.

Effects of dietary supplementation with purple garlic powder and oregano essential oil on intestinal health in post-weaning piglets from commercial farms

This work studied the effects of the inclusion of Purple Garlic Powder (PGP) and Oregano Essential Oil (OEO) in the feed, at different doses and combinations, on intestinal health and the growth performance of 140 and 3000 piglets, respectively, weaned at 21 days of age. Seven dietary treatments were used: a negative control group (basal diet), a positive control group with ZnO (3000 mg/Kg of feed), two groups with OEO at 0.4% and 1.2% respectively, two groups with PGP at 0.4% and 2% respectively and one group with OEO at 1.2% combined with PGP at 2%. Only the positive control group received ZnO in the diet. Each group of piglets received the treatment for seven weeks, from weaning, and were later sacrificed to obtain jejunum and ileum samples for counting of goblet cells, intraepithelial lymphocytes, and IgA-producing cells. The growth performance were measured at the beginning and at the end of the seven weeks. In jejunum and ileum, the number of goblet cells increased in the groups with ZnO, PGP 2%, OEO 1.2% and PGP 2% + OEO 1.2%, presenting significant differences with the rest of the groups. The results obtained for the intraepithelial lymphocyte count were in line with those obtained for the count of goblet cells. Regarding IgA-producing cells, the groups that showed significantly favourable results in the jejunum and ileum were OEO 1.2%, PGP 2% and their combination, but the groups that showed the most similar means to ZnO were the OEO 0.4% and the PGP 0.4%. Regarding the growth performance, PGP 2%, OEO 1.2% and their combination had similar results to ZnO. The intestinal health of piglets could be improved, without harming the growth performance, by means of the supplementation of PGP 2%, OEO 1.2% and PGP 2% + OEO 1.2% offering a natural alternative to the use of ZnO.