Enteric Microbiota Research Articles

Correlation between gastrointestinal morphological changes, enteric microbiota, and changes in live weight in dairy calves

This study aimed to quantify the association between fecal microbiota biomarkers, gastrointestinal tract (GIT) morphology, and average daily gain (ADG) of dairy calves from birth until weaned in response to feeding a direct-fed microbial (DFM) supplement as part of their milk diet. Forty-four newborn Holstein-Friesian calves were randomly assigned to Treatment (TRT) and Control (CON) groups. The TRT group calves received a once-daily dose of Lacticaseibacillus and Lentilactobacilli-based direct-fed microbial (DFM) liquid formulation. Four genera: Prevotella7, Succiniclasticum, Terrisporobacter, and Carnobacterium were enriched and identified as biomarkers of low ADG. Fourteen bacterial taxa were associated with measured gastrointestinal histopathology variables in TRT and CON groups. Although this study lists several bacterial taxa that have known roles in fermentation and nutrient metabolism vital for rumen function, their specific contributions to gastrointestinal development and weight gain remain to be fully understood. Our findings support a strategic approach to probiotic use in heifers to boost health and productivity.

Paclitaxel chemotherapy disrupts microbiota-enterohepatic bile acid metabolism in mice

ABSTRACT Balanced interactions between the enteric microbiota and enterohepatic organs are essential to bile acid homeostasis, and thus normal gastrointestinal function. Disruption of these interactions by cancer treatment instigates bile acid malabsorption, leading to treatment delays, malnutrition, and decreased quality of life. However, the nature of chemotherapy-induced bile acid malabsorption remains poorly characterized with limited treatment options. Therefore, this study sought to characterize changes in hepatic, enteric, and microbial bile acid metabolism in a mouse model of chemotherapy-induced toxicity. Consistent with clinical bile acid malabsorption, chemotherapy increased fecal excretion of primary bile acids and water, while diminishing microbiome diversity, secondary bile acid formation, and small intestinal bile acid signaling. We identified new contributors to pathology of bile acid malabsorption in the forms of lipopolysaccharide-induced cholestasis and colonic crypt hyperplasia from reduced secondary bile acid signaling. Chemotherapy reduced markers of hepatic bile flow and bile acid synthesis, elevated markers of fibrosis and endotoxemia, and altered transcription of genes at all stages of bile acid metabolism. Primary hepatocytes exposed to lipopolysaccharide (but not chemotherapy) replicated chemotherapy-induced transcriptional differences, while gut microbial transplant into germ-free mice replicated very few differences. In the colon, chemotherapy-altered bile acid profiles (particularly higher tauromuricholic acid and lower hyodeoxycholic acid) coincided with crypt hyperplasia. Exposing primary colonoids to hyodeoxycholic acid reduced proliferation, while gut microbiota transplant enhanced proliferation. Together, these investigations reveal complex involvement of the entire microbiota-enterohepatic axis in chemotherapy-induced bile acid malabsorption. Interventions to reduce hepatic lipopolysaccharide exposure and enhance microbial bile acid metabolism represent promising co-therapies to cancer treatment.

Multi-omics analysis reveals regime shifts in the gastrointestinal ecosystem in chickens following anticoccidial vaccination and Eimeria tenella challenge.

Coccidiosis, caused by Eimeria parasites, significantly impacts poultry farm economics and animal welfare. Beyond its direct impact on health, Eimeria infection disrupts enteric microbial populations leading to dysbiosis and increases vulnerability to secondary diseases such as necrotic enteritis, caused by Clostridium perfringens. The impact of Eimeria infection or anticoccidial vaccination on host gastrointestinal phenotypes and enteric microbiota remains understudied. In this study, the metabolomic profiles and microbiota composition of chicken caecal tissue and contents were evaluated concurrently during a controlled experimental vaccination and challenge trial. Cobb500 broilers were vaccinated with a Saccharomyces cerevisiae-vectored anticoccidial vaccine and challenged with 15,000 Eimeria tenella oocysts. Assessment of caecal pathology and quantification of parasite load revealed correlations with alterations to caecal microbiota and caecal metabolome linked to infection and vaccination status. Infection heightened microbiota richness with increases in potentially pathogenic species, while vaccination elevated beneficial Bifidobacterium. Using a multi-omics factor analysis, data on caecal microbiota and metabolome were integrated and distinct profiles for healthy, infected, and recovering chickens were identified. Healthy and recovering chickens exhibited higher vitamin B metabolism linked to short-chain fatty acid-producing bacteria, whereas essential amino acid and cell membrane lipid metabolisms were prominent in infected and vaccinated chickens. Notably, vaccinated chickens showed distinct metabolites related to the enrichment of sphingolipids, important components of nerve cells and cell membranes. Our integrated multi-omics model revealed latent biomarkers indicative of vaccination and infection status, offering potential tools for diagnosing infection, monitoring vaccination efficacy, and guiding the development of novel treatments or controls.IMPORTANCEAdvances in anticoccidial vaccines have garnered significant attention in poultry health management. However, the intricacies of vaccine-induced alterations in the chicken gut microbiome and its subsequent impact on host metabolism remain inadequately explored. This study delves into the metabolic and microbiotic shifts in chickens post-vaccination, employing a multi-omics integration analysis. Our findings highlight a notable synergy between the microbiome composition and host-microbe interacted metabolic pathways in vaccinated chickens, differentiating them from infected or non-vaccinated cohorts. These insights pave the way for more targeted and efficient approaches in poultry disease control, enhancing both the efficacy of vaccines and the overall health of poultry populations.

Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis.

HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger of axSpA. We recently identified a bacterial peptide (YeiH) that can be presented by HLA-B*27 to expanded public T cell receptors in the joint in axSpA and the eye in B27AAU. While YeiH is present in enteric microbiota and pathogens, additional evidence that pathogenic T cells in HLA-B*27-associated autoimmunity may have had a prior antigenic encounter within the gastrointestinal tract remains lacking. Here, we analyzed ocular, synovial, and blood T cells in B27AAU and axSpA, showing that YeiH-specific CD8+ T cells express a mucosal gene set and surface proteins consistent with intestinal differentiation, including CD161, integrin α4β7, and CCR6. In addition, we found an expansion of YeiH-specific CD8+ T cells in axSpA and B27AAU blood compared with that from individuals acting as healthy controls, whereas influenza-specific CD8+ T cells were equivalent across groups. Finally, we demonstrated the dispensability of TRBV9 for antigen recognition. Collectively, our data suggest that, in HLA-B27-associated autoimmunity, early antigen exposure and differentiation of pathogenic CD8+ T cells may occur in enteric organs.

Mitochondrial function and gastrointestinal diseases.

Mitochondria are dynamic organelles that function in cellular energy metabolism, intracellular and extracellular signalling, cellular fate and stress responses. Mitochondria of the intestinal epithelium, the cellular interface between self and enteric microbiota, have emerged as crucial in intestinal health. Mitochondrial dysfunction occurs in gastrointestinal diseases, including inflammatory bowel diseases and colorectal cancer. In this Review, we provide an overview of the current understanding of intestinal epithelial cell mitochondrial metabolism, function and signalling to affect tissue homeostasis, including gut microbiota composition. We also discuss mitochondrial-targeted therapeutics for inflammatory bowel diseases and colorectal cancer and the evolving concept of mitochondrial impairment as a consequence versus initiator of the disease.

The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.

Longitudinal evaluation of the cutaneous and rectal microbiota of German shepherd dogs with perianal fistulas undergoing therapy with ciclosporin and ketoconazole.

Perianal fistulas are painful ulcers or sinus tracts that disproportionately affect German shepherd dogs and are proposed as a spontaneous animal model of fistulising Crohn's disease. To characterise the rectal and cutaneous microbiota in German shepherd dogs with perianal fistulas and to investigate longitudinal shifts with lesion resolution during immunomodulatory therapy. Eleven German shepherd dogs with perianal fistulas and 15 healthy German shepherd dogs. Affected dogs were evaluated and swabbed at three visits, 30 days apart, while undergoing treatment with ciclosporin and ketoconazole. Healthy German shepherd dogs were contemporaneously sampled. Sites included the rectum, perianal skin and axilla. The microbiome was evaluated following sequencing of the V4 hypervariable region of the 16S ribosomal RNA (rRNA) gene. Alpha diversity was not significantly different between healthy and affected dogs at each of the three body sites (p > 0.5), yet rectal and perianal beta diversities from affected dogs differed significantly from those of healthy dogs at Day 0 (p = 0.004). Rectal and perianal relative abundance of Prevotella spp. increased and perianal Staphylococcus spp. relative abundance decreased in affected dogs over time, coincident with lesion resolution. Changes in lesional cutaneous and rectal microbiota occur in German shepherd dogs with perianal fistulas and shift over time with lesion resolution during immunomodulatory therapy. Further investigations of the role of cutaneous and enteric microbiota in the pathogenesis of perianal fistulas, and whether manipulation of microbial populations may ameliorate disease, are needed.

The application of High-Resolution Nuclear Magnetic Resonance (HR NMR) in metabolomic analyses of meconium and stool in newborns. A preliminary pilot study of MABEL project: Metabolomics approach for the assessment of Baby-Mother Enteric Microbiota Legacy

BackgroundThe microbial population living in our intestines plays a key role in several metabolic, nutritional, physiological, and immunological processes. It is known that infant gut microbiota composition has both horizontal transmission delivery and environmental conditions and a vertical one, from mother to child, related to how the infant is fed (breastfed or infant formula). Detailed information on the composition of meconium and feces from newborns may help predict the most prevalent and hazardous conditions affecting pregnancies, mothers, and babies, including pre-term birth, preeclampsia, and gestational diabetes mellitus for example. MethodsThis work aims to demonstrate the feasibility of the whole High-Resolution proton Nuclear Magnetic Resonance (1H HR NMR) procedure in metabolomic analysis in preterm newborns. Thus, multiple samples of meconium and stool were collected from 3 pairs of premature twins and their metabolite profiles were acquired and exploited by combining the NMR technique with univariate and multivariate analysis. ResultsThe analysis showed that an impact on the metabolite profile was visible concerning both the sex of the newborns and the couplet of origin. Most of the variation between twin couplets was seen with butyric acid concentration in meconium/stool samples. ConclusionsDespite the low number of samples, the described NMR procedure showed to be a suitable approach to evaluate the similarities of the molecular profiles of different samples, offering a non-invasive and informative approach to understanding the metabolic and nutritional status of preterm infants. Future metabolomic analysis should be supported by microbiome analysis, such multiomic approach will provide more complex view on development of preterm newborns.

Minding the gut: extending embodied cognition and perception to the gut complex.

Scientific and philosophical accounts of cognition and perception have traditionally focused on the brain and external sense organs. The extended view of embodied cognition suggests including other parts of the body in these processes. However, one organ has often been overlooked: the gut. Frequently conceptualized as merely a tube for digesting food, there is much more to the gut than meets the eye. Having its own enteric nervous system, sometimes referred to as the "second brain," the gut is also an immune organ and has a large surface area interacting with gut microbiota. The gut has been shown to play an important role in many physiological processes, and may arguably do so as well in perception and cognition. We argue that proposals of embodied perception and cognition should take into account the role of the "gut complex," which considers the enteric nervous, endocrine, immune, and microbiota systems as well as gut tissue and mucosal structures. The gut complex is an interface between bodily tissues and the "internalized external environment" of the gut lumen, involved in many aspects of organismic activity beyond food intake. We thus extend current embodiment theories and suggest a more inclusive account of how to "mind the gut" in studying cognitive processes.

Chronic Inflammatory Enteropathy and Low-Grade Intestinal T-Cell Lymphoma Are Associated with Altered Microbial Tryptophan Catabolism in Cats.

Chronic inflammatory enteropathy (CIE) and low-grade intestinal T-cell lymphoma (LGITL) are common chronic enteropathies (CE) in cats. Enteric microbiota dysbiosis is implicated in the pathogenesis of CE; however, the mechanisms of host-microbiome interactions are poorly understood in cats. Microbial indole catabolites of tryptophan (MICT) are gut bacterial catabolites of tryptophan that are hypothesized to regulate intestinal inflammation and mucosal barrier function. MICTs are decreased in the sera of humans with inflammatory bowel disease and previous studies identified altered tryptophan metabolism in cats with CE. We sought to determine whether MICTs were decreased in cats with CE using archived serum samples from cats with CIE (n = 44) or LGITL (n = 31) and healthy controls (n = 26). Quantitative LC-MS/MS was used to measure serum concentrations of tryptophan, its endogenous catabolites (kynurenine, kynurenate, serotonin) and MICTs (indolepyruvate, indolealdehyde, indoleacrylate, indoleacetamide, indoleacetate, indolelactate, indolepropionate, tryptamine). Serum concentrations of tryptophan, indolepropionate, indoleacrylate, indolealdehyde, indolepyruvate, indolelactate were significantly decreased in the CIE and LGITL groups compared to those in healthy controls. Indolelactate concentrations were significantly lower in cats with LGITL compared to CIE (p = 0.006). Significant correlations were detected among serum MICTs and cobalamin, folate, fPLI, and fTLI. Our findings suggest that MICTs are promising biomarkers to investigate the role of gut bacteria in the pathobiology of chronic enteropathies in cats.

Anti-allergic effects of Ulva-derived polysaccharides, oligosaccharides and residues in a murine model of food allergy

The medicinal benefits of green seaweed Ulva have been documented in traditional Chinese medicine literatures. Sulfated polysaccharides found in Ulva are recognized as the primary bioactive compounds, known for their immunomodulatory and anti-inflammatory properties. Despite this knowledge, the available information regarding anti-allergic activities of Ulva remains limited. The objective of this study was to prepare and characterize Ulva-derived polysaccharides (UP), oligosaccharides (UO), and residues (UR), followed by assessing their potential in improving allergic enteritis and gut microbiota in a murine model of ovalbumin (OVA)-induced food allergy. The immunomodulatory activities of UP, UO, and UR were evaluated by measuring the expression of serum antibodies, splenic cytokines and duodenal transcript factors of T cell subsets. The impact of UP, UO, and UR on enteric microbiota was explored by 16S rRNA gene sequencing analysis of fresh fecal samples from treated mice. Oral treatment of UP, UO, and UR noticeably attenuated allergic diarrhea and enteritis. Additionally, Ulva samples treatment decreased serum levels of IgG1 and OVA-specific IgE while increased the level of OVA-specific IgG. Enhanced production of IFN-γ and reduced production of IL-4 and IL-10 by splenocytes were observed in the treated mice. In parallel, Ulva samples treatment led to a decreased number of GATA3+ cells and an increased number of T-bet+ cells in the duodenum. However, the population of Foxp3+ cells was not significantly altered. Moreover, treatment of Ulva samples improved enteric dysbiosis evidenced by an increased abundance of Lactobacillus murinus, L. johnsonii, and L. reuteri, and a decreased abundance of Kineothrix alysoides, Lacrimispora saccharolytica, L. aerotolerans, and Erysipelotrichaceae in feces. In conclusion, UP, UO, and UR, which could modulate the Th1/Th2 immune balance, alleviate allergic enteritis and improve enteric dysbiosis in varying degrees, are potential to be developed into therapeutic agents for food allergy.

Exocrine pancreatic insufficiency in dogs and cats.

Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome caused by insufficient secretion of digestive enzymes from pancreatic acini. The most common causes of EPI in dogs and cats are pancreatic acinar atrophy and chronic pancreatitis. EPI is diagnosed by measurement of species-specific immunoassays for serum trypsin-like immunoreactivity, the concentration of which directly reflects the mass of functioning pancreatic acinar tissue. EPI is treated by pancreatic enzyme replacement therapy, nutritional management (low-residue diets with moderate fat content), and supplementation of cobalamin. Some dogs and cats have persistent clinical signs despite these treatments. Growing evidence suggests that these clinical signs may be due to enteric microbiota dysbiosis or the presence of concurrent diseases such as chronic enteropathies. Management of these abnormalities may improve outcome in dogs and cats with EPI. The long-term prognosis for dogs and cats with EPI is generally good if high-quality medical therapy is provided. Future studies are needed to further understand the causes of persistent dysbiosis in animals with EPI following initiation of pancreatic enzyme replacement therapy and assess the efficacy of treatments to ameliorate these abnormalities.

Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

ObjectivesThis study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microbiota by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. MethodsIn vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. ResultsNicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. ConclusionsNicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

Decoding the role of gut microbiota in Alzheimer's pathogenesis and envisioning future therapeutic avenues.

Alzheimer's disease (AD) emerges as a perturbing neurodegenerative malady, with a profound comprehension of its underlying pathogenic mechanisms continuing to evade our intellectual grasp. Within the intricate tapestry of human health and affliction, the enteric microbial consortium, ensconced within the milieu of the human gastrointestinal tract, assumes a role of cardinal significance. Recent epochs have borne witness to investigations that posit marked divergences in the composition of the gut microbiota between individuals grappling with AD and those favored by robust health. The composite vicissitudes in the configuration of the enteric microbial assembly are posited to choreograph a participatory role in the inception and progression of AD, facilitated by the intricate conduit acknowledged as the gut-brain axis. Notwithstanding, the precise nature of this interlaced relationship remains enshrouded within the recesses of obscurity, poised for an exhaustive revelation. This review embarks upon the endeavor to focalize meticulously upon the mechanistic sway exerted by the enteric microbiota upon AD, plunging profoundly into the execution of interventions that govern the milieu of enteric microorganisms. In doing so, it bestows relevance upon the therapeutic stratagems that form the bedrock of AD's management, all whilst casting a prospective gaze into the horizon of medical advancements.

Brazil Nut-Enriched Diet Modulates Enteric Glial Cells and Gut Microbiota in an Experimental Model of Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.

Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.

Coronavirus disease 2019 (COVID-19) has been demonstrated to affect several systems of the human body, including the gastrointestinal and nervous systems. The enteric nervous system (ENS) is a division of the autonomic nervous system that extends throughout the gut, regulates gastrointestinal function, and is therefore involved in most gut dysfunctions, including those resulting from many viral infections. Growing evidence highlights enteric neural cells and microbiota as important players in gut inflammation and dysfunction. Furthermore, the ENS and gastrointestinal immune system work together establishing relevant neuroimmune interactions during both health and disease. In recent years, gut-driven processes have also been implicated as players in systemic inflammation and in the initiation and propagation of several central nervous system pathologies, which seem to be hallmarks of COVID-19. In this review, we aim to describe evidence of the gastrointestinal and ENS infection with a focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss here viral-induced mechanisms, neuroplasticity, and neuroinflammation to call attention to the enteric neuroglial network as a nervous system with a sensitive and crucial position to be not only a target of the new coronavirus but also a way in and trigger of COVID-19-related symptoms.

Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure.

Alcohol exposure in adulthood can result in inflammation, malnutrition, and altered gastroenteric microbiota, which may disrupt efficient nutrient extraction. Clinical and preclinical studies have documented convincingly that prenatal alcohol exposure (PAE) also results in persistent inflammation and nutrition deficiencies, though research on the impact of PAE on the enteric microbiota is in its infancy. Importantly, other neurodevelopmental disorders, including autism spectrum and attention deficit/hyperactivity disorders, have been linked to gut microbiota dysbiosis. The combined evidence from alcohol exposure in adulthood and from other neurodevelopmental disorders supports the hypothesis that gut microbiota dysbiosis is likely an etiological feature that contributes to negative developmental, including neurodevelopmental, consequences of PAE and results in fetal alcohol spectrum disorders. Here, we highlight published data that support a role for gut microbiota in healthy development and explore the implication of these studies for the role of altered microbiota in the lifelong health consequences of PAE.

Single Cell Sequencing Suggests Mucosal Origins of T Cells in HLA-B27-associated Inflammation

Abstract HLA-B27 was one of the first Major Histocompatibility Complex alleles associated with an autoimmune disease, i.e., Ankylosing Spondylitis (AS) and acute anterior uveitis (B27AU), which cause joint and eye inflammation, respectively. As HLA-B27 presents antigens to CD8 T cells, an antigen-specific CD8 T cell response may be central to disease pathogenesis. Consistent with this hypothesis, our recent work identified clonal expansion of public T cell receptors (TCRs) shared across patients with AS and B27AU and enriched in the joint or eye over the blood. These TCRs recognized both bacterial and self-peptides, suggesting a role for molecular mimicry in multiple organs afflicted by HLA-B27-associated inflammation. The main bacterial peptide recognized by these public TCRs is derived from yeiH, a gene present in multiple enteric microbiota. It remains unclear, however, whether these T cells have had a prior antigenic encounter within the gastrointestinal tract. We therefore performed single-cell RNA sequencing (scRNAseq) and T cell receptor sequencing (scTCRseq) on immune cells from the eye and blood during B27AU (n=5) and non-B27AU (n=14). In this analysis, we found that the expanded TCRs in B27AU were associated with CD161 expression and enriched for a transcriptional program from intestinal CD8 T cells. Moreover, we were able to identify an additional expanded TCR sequence that also recognized YEIH. Finally, expanded T cell clones contained higher expression of TNFand IFNG, suggestive of a pro-inflammatory transcriptional program. Collectively, our data suggest that, in HLA-B27-associated inflammation, the early antigen exposure and differentiation of putative pathogenic CD8 T cells may have occurred in enteric organs. This study received support from NIH 5R01AI103867 (KCG), U19AI057229 (KCG), the Howard Hughes Medical Institute (KCG), the Rheumatology Research Foundation (MAP), Arthritis National Research Foundation (MAP), the Rheumatic Diseases Research Resource-based Center at Washington University (NIH P30-AR073752, MAP, WMY), the Bursky Center for Human Immunology and Immunotherapy Programs (WMY), and the Barnes-Jewish Hospital Foundation (WMY).

Connecting the Dots: The Interplay Between Stroke and the Gut-Brain Axis.

This article discusses the interplay between the gut-brain axis and stroke, a multifaceted neurological disorder that affects millions of people worldwide. The gut-brain axis is a bidirectional communication network linking the central nervous system (CNS) to the gastrointestinal tract (GIT), including the enteric nervous system (ENS), vagus nerve, and gut microbiota. Dysbiosis in the gut microbiota, alterations in the ENS and vagus nerve, and gut motility changes have been linked to increased inflammation and oxidative stress, which are contributing factors in the development and progression of stroke. Research on animals has shown that modifying the gut microbiota can impact the results of a stroke. Germ-free mice displayed improved neurological function and decreased infarct volumes, indicating a positive effect. Furthermore, studies in stroke patients have shown alterations in the gut microbiota composition, indicating that targeting dysbiosis could be a potential therapeutic strategy for stroke. The review suggests that targeting the gut-brain axis may represent a potential therapeutic approach to reduce the morbidity and mortality associated with stroke.

Antimicrobial Growth Promoters Altered the Function but Not the Structure of Enteric Bacterial Communities in Broiler Chicks ± Microbiota Transplantation.

Non-antibiotic alternatives to antimicrobial growth promoters (AGPs) are required, and understanding the mode of action of AGPs may facilitate the development of effective alternatives. The temporal impact of the conventional antibiotic AGP, virginiamycin, and an AGP alternative, ceragenin (CSA-44), on the structure and function of the broiler chicken cecal microbiota was determined using next-generation sequencing and 1H-nuclear magnetic resonance spectroscopy (NMR)-based metabolomics. To elucidate the impact of enteric bacterial diversity, oral transplantation (±) of cecal digesta into 1-day-old chicks was conducted. Microbiota transplantation resulted in the establishment of a highly diverse cecal microbiota in recipient chicks that did not change between day 10 and day 15 post-hatch. Neither virginiamycin nor CSA-44 influenced feed consumption, weight gain, or feed conversion ratio, and did not affect the structure of the cecal microbiota in chicks possessing a low or high diversity enteric microbiota. However, metabolomic analysis of the cecal contents showed that the metabolome of cecal digesta was affected in birds administered virginiamycin and CSA-44 as a function of bacterial community diversity. As revealed by metabolomics, glycolysis-related metabolites and amino acid synthesis pathways were impacted by virginiamycin and CSA-44. Thus, the administration of AGPs did not influence bacterial community structure but did alter the function of enteric bacterial communities. Hence, alterations to the functioning of the enteric microbiota in chickens may be the mechanism by which AGPs impart beneficial health benefits, and this possibility should be examined in future research.