Torque Teno Virus: A Promising Biomarker in Kidney Transplant Recipients.

Torque Teno Virus (TTV) is a ubiquitous component of the human virome, not associated with any disease. As its load increases when the immune system is compromised, such as in kidney transplant (KT) recipients, TTV load monitoring has been proposed as a method to assess immunosuppression. In this prospective study, TTV load was measured in plasma and urine samples from 42 KT recipients, immediately before KT and in the first 150 days after it. Data obtained suggest that TTV could be a relevant marker for evaluating immune status and could be used as a guide to predict the onset of infectious complications in the follow-up of KT recipients. Since we observed no differences considering distance from transplantation, while we found a changing trend in days before viral infections, we suggest to consider changes over time in the same subjects, irrespective of time distance from transplantation.

OTX Genes in Adult Tissues.

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets.

Hyaluronan in pathophysiology of vascular diseases: specific roles in smooth muscle cells, endothelial cells, and macrophages.

One of the main components of the extracellular matrix (ECM) of blood vessels is hyaluronic acid or hyaluronan (HA). It is a ubiquitous polysaccharide belonging to the family of glycosaminoglycans, but, differently from other proteoglycan-associated glycosaminoglycans, it is synthesized on the plasma membrane by a family of three HA synthases (HAS). HA can be released as a free polymer in the extracellular space or remain associated with the plasma membrane in the pericellular space via HAS or HA-binding proteins. Several cell surface proteins can interact with HA working as HA receptors, like CD44, RHAMM, and LYVE-1. In physiological conditions, HA is localized in the glycocalyx and the adventitia where it is responsible for the loose and hydrated vascular structure favoring flexibility and allowing the stretching of vessels in response to mechanical forces. During atherogenesis, ECM undergoes dramatic alterations that have a crucial role in lipoprotein retention and in triggering multiple signaling cascades that induce the cells to exit from their quiescent status. HA becomes highly present in the media and neointima favoring smooth muscle cells dedifferentiation, migration, and proliferation that strongly contribute to vessel wall thickening. Furthermore, HA is able to modulate immune cell recruitment both within the vessel wall and on the endothelial cell layer. This review is focused on deeply analyzing the effects of HA on vascular cell behavior.

Microbiota medicine: towards clinical revolution.

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.

Soy diet induces intestinal inflammation in adult Zebrafish: Role of OTX and P53 family.

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the colon and small intestine, including Crohn's disease and ulcerative colitis. Since Danio rerio is a promising animal model to study gut function, we developed a soy-dependent model of intestinal inflammation in adult zebrafish. The soya bean meal diet was given for 4 weeks and induced an inflammatory process, as demonstrated by morphological changes together with an increased percentage of neutrophils infiltrating the intestinal wall, which developed between the second and fourth week of treatment. Pro-inflammatory genes such as interleukin-1beta, interleukin-8 and tumour necrosis factor alpha were upregulated in the second week and anti-inflammatory genes such as transforming growth factor beta and interleukin-10. Interestingly, an additional expression peak was found for interleukin-8 at the fourth week. Neuronal genes, OTX1 and OTX2, were significantly upregulated in the first two  weeks, compatible with the development of the changes in the gut wall. As for the genes of the p53 family such as p53, DNp63 and p73, a statistically significant increase was observed after two weeks of treatment compared with controls. Interestingly, DNp63 and p73 were shown an additional peak after four weeks. Our data demonstrate that soya bean meal diet negatively influences intestinal morphology and immunological function in adult zebrafish showing the features of acute inflammation. Data observed at the fourth week of treatment may suggest initiation of chronic inflammation. Adult zebrafish may represent a promising model to better understand the mechanisms of food-dependent intestinal inflammation.

Bacterial pigments: A colorful palette reservoir for biotechnological applications.

Synthetic derivatives are currently used instead of pigments in many applicative fields, from food to feed, from pharmaceutical to diagnostic, from agronomy to industry. Progress in organic chemistry allowed to obtain rather cheap compounds covering the whole color spectrum. However, several concerns arise from this chemical approach, as it is mainly based on nonrenewable resources such as fossil oil, and the toxicity or carcinogenic properties of products and/or precursors may be harmful for personnel involved in the productive processes. In this scenario, microorganisms and their pigments represent a colorful world to discover and reconsider. Each living bacterial strain may be a source of secondary metabolites with peculiar functions. The aim of this review is to link the physiological role of bacterial pigments with their potential use in different biotechnological fields. This enormous potential supports the big challenge for the development of strategies useful to identify, produce, and purify the right pigment for the desired application. At the end of this ideal journey through the world of bacterial pigments, the attention will be focused on melanin compounds, whose production relies upon different techniques ranging from natural producers, heterologous hosts, or isolated enzymes. In a green workflow, the microorganisms represent the starting and final point of pigment production.

Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease.

The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.

TRPV4 channels' dominant role in the temperature modulation of intrinsic contractility and lymph flow of rat diaphragmatic lymphatics.

The lymphatic system drains and propels lymph by extrinsic and intrinsic mechanisms. Intrinsic propulsion depends upon spontaneous rhythmic contractions of lymphatic muscles in the vessel walls and is critically affected by changes in the surrounding tissue like osmolarity and temperature. Lymphatics of the diaphragm display a steep change in contraction frequency in response to changes in temperature, and this, in turn, affects lymph flow. In the present work, we demonstrated in an ex vivo diaphragmatic tissue rat model that diaphragmatic lymphatics express transient receptor potential channels of the vanilloid 4 subfamily (TRPV4) and that their blockade by both the nonselective antagonist Ruthenium Red and the selective antagonist HC-067047 abolished the response of lymphatics to temperature changes. Moreover, the selective activation of TRPV4 channels by means of GSK1016790A mirrored the behavior of vessels exposed to increasing temperatures, pointing out the critical role played by these channels in sensing the temperature of the lymphatic vessels' environment and thus inducing a change in contraction frequency and lymph flow.NEW & NOTEWORTHY The present work addresses the putative receptor system that enables diaphragmatic lymphatics to change intrinsic contraction frequency and thus lymph flow according to the changes in temperature of the surrounding environment, showing that this role can be sustained by TRPV4 channels alone.

Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis.

A complex bidirectional communication system exists between the gastrointestinal tract and the brain. Initially termed the "gut-brain axis" it is now renamed the "microbiota-gut-brain axis" considering the pivotal role of gut microbiota in maintaining local and systemic homeostasis. Different cellular and molecular pathways act along this axis and strong attention is paid to neuroactive molecules (neurotransmitters, i.e., noradrenaline, dopamine, serotonin, gamma aminobutyric acid and glutamate and metabolites, i.e., tryptophan metabolites), sustaining a possible interkingdom communication system between eukaryota and prokaryota. This review provides a description of the most up-to-date evidence on glutamate as a neurotransmitter/neuromodulator in this bidirectional communication axis. Modulation of glutamatergic receptor activity along the microbiota-gut-brain axis may influence gut (i.e., taste, visceral sensitivity and motility) and brain functions (stress response, mood and behavior) and alterations of glutamatergic transmission may participate to the pathogenesis of local and brain disorders. In this latter context, we will focus on two major gut disorders, such as irritable bowel syndrome and inflammatory bowel disease, both characterized by psychiatric co-morbidity. Research in this area opens the possibility to target glutamatergic neurotransmission, either pharmacologically or by the use of probiotics producing neuroactive molecules, as a therapeutic approach for the treatment of gastrointestinal and related psychiatric disorders.

The ecto-enzymes CD73 and adenosine deaminase modulate 5'-AMP-derived adenosine in myofibroblasts of the rat small intestine.

Adenosine is a versatile signaling molecule recognized to physiologically influence gut motor functions. Both the duration and magnitude of adenosine signaling in enteric neuromuscular function depend on its availability, which is regulated by the ecto-enzymes ecto-5'-nucleotidase (CD73), alkaline phosphatase (AP), and ecto-adenosine deaminase (ADA) and by dipyridamole-sensitive equilibrative transporters (ENTs). Our purpose was to assess the involvement of CD73, APs, ecto-ADA in the formation of AMP-derived adenosine in primary cultures of ileal myofibroblasts (IMFs). IMFs were isolated from rat ileum longitudinal muscle segments by means of primary explant technique and identified by immunofluorescence staining for vimentin and α-smooth muscle actin. IMFs confluent monolayers were exposed to exogenous 5'-AMP in the presence or absence of CD73, APs, ecto-ADA, or ENTs inhibitors. The formation of adenosine and its metabolites in the IMFs medium was monitored by high-performance liquid chromatography. The distribution of CD73 and ADA in IMFs was detected by confocal immunocytochemistry and qRT-PCR. Exogenous 5'-AMP was rapidly cleared being almost undetectable after 60-min incubation, while adenosine levels significantly increased. Treatment of IMFs with CD73 inhibitors markedly reduced 5'-AMP clearance whereas ADA blockade or inhibition of both ADA and ENTs prevented adenosine catabolism. By contrast, inhibition of APs did not affect 5'-AMP metabolism. Immunofluorescence staining and qRT-PCR analysis confirmed the expression of CD73 and ADA in IMFs. Overall, our data show that in IMFs an extracellular AMP-adenosine pathway is functionally active and among the different enzymatic pathways regulating extracellular adenosine levels, CD73 and ecto-ADA represent the critical catabolic pathway.

Nitric oxide regulates homeoprotein OTX1 and OTX2 expression in the rat myenteric plexus after intestinal ischemia-reperfusion injury.

Neuronal and inducible nitric oxide synthase (nNOS and iNOS) play a protective and damaging role, respectively, on the intestinal neuromuscular function after ischemia-reperfusion (I/R) injury. To uncover the molecular pathways underlying this dichotomy we investigated their possible correlation with the orthodenticle homeobox proteins OTX1 and OTX2 in the rat small intestine myenteric plexus after in vivo I/R. Homeobox genes are fundamental for the regulation of the gut wall homeostasis both during development and in pathological conditions (inflammation, cancer). I/R injury was induced by temporary clamping the superior mesenteric artery under anesthesia, followed by 24 and 48 h of reperfusion. At 48 h after I/R intestinal transit decreased and was further reduced by Nω-propyl-l-arginine hydrochloride (NPLA), a nNOS-selective inhibitor. By contrast this parameter was restored to control values by 1400W, an iNOS-selective inhibitor. In longitudinal muscle myenteric plexus (LMMP) preparations, iNOS, OTX1, and OTX2 mRNA and protein levels increased at 24 and 48 h after I/R. At both time periods, the number of iNOS- and OTX-immunopositive myenteric neurons increased. nNOS mRNA, protein levels, and neurons were unchanged. In LMMPs, OTX1 and OTX2 mRNA and protein upregulation was reduced by 1400W and NPLA, respectively. In myenteric ganglia, OTX1 and OTX2 staining was superimposed with that of iNOS and nNOS, respectively. Thus in myenteric ganglia iNOS- and nNOS-derived NO may promote OTX1 and OTX2 upregulation, respectively. We hypothesize that the neurodamaging and neuroprotective roles of iNOS and nNOS during I/R injury in the gut may involve corresponding activation of molecular pathways downstream of OTX1 and OTX2.NEW & NOTEWORTHY Intestinal ischemia-reperfusion (I/R) injury induces relevant alterations in myenteric neurons leading to dismotility. Nitrergic neurons seem to be selectively involved. In the present study the inference that both neuronal and inducible nitric oxide synthase (nNOS and iNOS) expressing myenteric neurons may undergo important changes sustaining derangements of motor function is reinforced. In addition, we provide data to suggest that NO produced by iNOS and nNOS regulates the expression of the vital transcription factors orthodenticle homeobox protein 1 and 2 during an I/R damage.

Effects of Perinatal Antibiotic Exposure and Neonatal Gut Microbiota.

Antibiotic therapy is one of the most important strategies to treat bacterial infections. The overuse of antibiotics, especially in the perinatal period, is associated with long-lasting negative consequences such as the spread of antibiotic resistance and alterations in the composition and function of the gut microbiota, both of which negatively affect human health. In this review, we summarize recent evidence about the influence of antibiotic treatment on the neonatal gut microbiota and the subsequent negative effects on the health of the infant. We also analyze the possible microbiome-based approaches for the re-establishment of healthy microbiota in neonates.

Gut Microbiota, Inflammatory Bowel Disease, and Cancer: The Role of Guardians of Innate Immunity.

Inflammatory bowel diseases (IBDs) are characterized by a persistent low-grade inflammation that leads to an increased risk of colorectal cancer (CRC) development. Several factors are implicated in this pathogenetic pathway, such as innate and adaptive immunity, gut microbiota, environment, and xenobiotics. At the gut mucosa level, a complex interplay between the immune system and gut microbiota occurs; a disequilibrium between these two factors leads to an alteration in the gut permeability, called 'leaky gut'. Subsequently, an activation of several inflammatory pathways and an alteration of gut microbiota composition with a proliferation of pro-inflammatory bacteria, known as 'pathobionts', take place, leading to a further increase in inflammation. This narrative review provides an overview on the principal Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), focusing on their recognition mechanisms, signaling pathways, and contributions to immune responses. We also report the genetic polymorphisms of TLRs and dysregulation of NLR signaling pathways that can influence immune regulation and contribute to the development and progression of inflammatory disease and cancer.

The Microbiota-Gut Axis in Premature Infants: Physio-Pathological Implications.

Intriguing evidence is emerging in regard to the influence of gut microbiota composition and function on host health from the very early stages of life. The development of the saprophytic microflora is conditioned by several factors in infants, and peculiarities have been found for babies born prematurely. This population is particularly exposed to a high risk of infection, postnatal antibiotic treatment, feeding difficulties and neurodevelopmental disabilities. To date, there is still a wide gap in understanding all the determinants and the mechanism behind microbiota disruption and its influence in the development of the most common complications of premature infants. A large body of evidence has emerged during the last decades showing the existence of a bidirectional communication axis involving the gut microbiota, the gut and the brain, defined as the microbiota-gut-brain axis. In this context, given that very few data are available to demonstrate the correlation between microbiota dysbiosis and neurodevelopmental disorders in preterm infants, increasing interest has arisen to better understand the impact of the microbiota-gut-brain axis on the clinical outcomes of premature infants and to clarify how this may lead to alternative preventive, diagnostic and therapeutic strategies. In this review, we explored the current evidence regarding microbiota development in premature infants, focusing on the effects of delivery mode, type of feeding, environmental factors and possible influence of the microbiota-gut-brain axis on preterm clinical outcomes during their hospital stay and on their health status later in life.

Microbiota and Pain: Save Your Gut Feeling.

Recently, a growing body of evidence has emerged regarding the interplay between microbiota and the nervous system. This relationship has been associated with several pathological conditions and also with the onset and regulation of pain. Dysregulation of the axis leads to a huge variety of diseases such as visceral hypersensitivity, stress-induced hyperalgesia, allodynia, inflammatory pain and functional disorders. In pain management, probiotics have shown promising results. This narrative review describes the peripheral and central mechanisms underlying pain processing and regulation, highlighting the role of the gut-brain axis in the modulation of pain. We summarized the main findings in regard to the stress impact on microbiota's composition and its influence on pain perception. We also focused on the relationship between gut microbiota and both visceral and inflammatory pain and we provided a summary of the main evidence regarding the mechanistic effects and probiotics use.

Small intestine neuromuscular dysfunction in a mouse model of dextran sulfate sodium-induced ileitis: Involvement of dopaminergic neurotransmission.

AIMS: Anomalies in dopaminergic machinery have been shown in inflammatory bowel disease (IBD) patients and preclinical models of IBD. Thus, we aimed to evaluate the impact of dextran sodium sulfate (DSS)-induced ileitis on enteric dopaminergic pathways. MATERIALS AND METHODS: Male C57/Bl6 mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and were then switched to regular drinking water for 3 days. To measure ileitis severity inflammatory cytokines (IL-1ß, TNFα, IL-6) levels were assessed. Changes in ileal muscle tension were isometrically recorded following: 1) cumulative addition of dopamine on basal tone (0.1-1000 µM); ii) 4-Hz electric field stimulation (EFS) in the presence of 30 µM dopamine with/without 10 µM SCH-23390 (dopamine D1 receptor (D1R) antagonist) or 10 µM sulpiride (D2R antagonist). Immunofluorescence distribution of the neuronal HuC/D protein, glial S100ß marker, D1R, and dopamine transporter (DAT) were determined in longitudinal-muscle-myenteric plexus whole-mounts (LMMPs) by confocal microscopy. D1R and D2R mRNA transcripts were evaluated by qRT-PCR. KEY FINDINGS: DSS caused an inflammatory process in the small intestine associated to dysmotility and altered barrier permeability, as suggested by decreased fecal output and enhanced stool water content. DSS treatment caused a significant increase of DAT and D1R myenteric immunoreactivity as well as of D1R and D2R mRNA levels, accompanied by a significant reduction of dopamine-mediated relaxation, involving primarily D1-like receptors. SIGNIFICANCE: Mouse ileitis affects enteric dopaminergic neurotransmission mainly involving D1R-mediated responses. These findings provide novel information on the participation of dopaminergic pathways in IBD-mediated neuromuscular dysfunction.

Hyaluronan Regulates Neuronal and Immune Function in the Rat Small Intestine and Colonic Microbiota after Ischemic/Reperfusion Injury.

BACKGROUND: Intestinal ischemia and reperfusion (IRI) injury induces acute and long-lasting damage to the neuromuscular compartment and dysmotility. This study aims to evaluate the pathogenetic role of hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, as a modulator of the enteric neuronal and immune function and of the colonic microbiota during in vivo IRI in the rat small intestine. METHODS: mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h reperfusion. Injured, sham-operated and non-injured animals were treated with the HA synthesis inhibitor, 4-methylumbelliferone (4-MU 25 mg/kg). Fecal microbiota composition was evaluated by Next Generation Sequencing. Neutrophil infiltration, HA homeostasis and toll like receptor (TLR2 and TLR4) expression in the small intestine were evaluated by immunohistochemical and biomolecular approaches (qRT-PCR and Western blotting). Neuromuscular responses were studied in vitro, in the absence and presence of the selective TLR2/4 inhibitor, Sparstolonin B (SsnB 10, 30 µM). RESULTS: 4-MU significantly reduced IRI-induced enhancement of potentially harmful Escherichia and Enterococcus bacteria. After IRI, HA levels, neutrophil infiltration, and TLR2 and TLR4 expression were significantly enhanced in the muscularis propria, and were significantly reduced to baseline levels by 4-MU. In the injured, but not in the non-injured and sham-operated groups, SsnB reduced both electrical field-stimulated (EFS, 0.1-40 Hz) contractions and EFS-induced (10 Hz) non-cholinergic non-adrenergic relaxations. CONCLUSIONS: enhanced HA levels after intestinal IRI favors harmful bacteria overgrowth, increases neutrophil infiltration and promotes the upregulation of bacterial target receptors, TLR2 and TLR4, in the muscularis propria, inducing a pro-inflammatory state. TLR2 and TLR4 activation may, however, underlay a provisional benefit on excitatory and inhibitory neuronal pathways underlying peristalsis.

Effect of partial substitution of fishmeal with insect meal (Hermetia illucens) on gut neuromuscular function in Gilthead sea bream (Sparus aurata).

Alternative nutrient sources to fishmeal for fish feed, such as insect meals, represent a promising sustainable supply. However, the consequences for fish digestive function have not been exhaustively investigated. In the present study we evaluated the effect of partial fishmeal substitution with 10% Hermetia illucens (Hi10) larvae meal on the neuromuscular function of proximal and distal intestine in gilthead sea bream. In animals fed with insect meal, weight and growth parameters were similar to controls fed with conventional fishmeal. In addition, no anomalies in intestinal gross morphology and no overt signs of inflammation were observed. The gastrointestinal transit was significantly reduced in Hi10 fed animals. In the proximal and distal intestine longitudinal muscle, Hi10 feeding downregulated the excitatory cholinergic and serotoninergic transmission. Sodium nitroprusside-induced inhibitory relaxations increased in the proximal intestine and decreased in the distal intestine after Hi10 meal. Changes in the excitatory and inhibitory components of peristalsis were associated with adaptive changes in the chemical coding of both proximal and distal intestine myenteric plexus. However, these neuromuscular function alterations were not associated with considerable variations in morphometric growth parameters, suggesting that 10% Hi meal may represent a tolerable alternative protein source for gilthead sea bream diets.

Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System.

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/-) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100ß immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis.

The commensal microbiota plays a fundamental role in maintaining host gut homeostasis by controlling several metabolic, neuronal and immune functions. Conversely, changes in the gut microenvironment may alter the saprophytic microbial community and function, hampering the positive relationship with the host. In this bidirectional interplay between the gut microbiota and the host, hyaluronan (HA), an unbranched glycosaminoglycan component of the extracellular matrix, has a multifaceted role. HA is fundamental for bacterial metabolism and influences bacterial adhesiveness to the mucosal layer and diffusion across the epithelial barrier. In the host, HA may be produced and distributed in different cellular components within the gut microenvironment, playing a role in the modulation of immune and neuronal responses. This review covers the more recent studies highlighting the relevance of HA as a putative modulator of the communication between luminal bacteria and the host gut neuro-immune axis both in health and disease conditions, such as inflammatory bowel disease and ischemia/reperfusion injury.