Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis

Bosi, Annalisa; Banfi, Davide; Bistoletti, Michela; Moretto, Paola; Moro, Elisabetta; Crema, Francesca; Maggi, Fabrizio; Karousou, Evgenia; Viola, Manuela; Passi, Alberto; Vigetti, Davide; Giaroni, Cristina; Baj, Andreina

doi:10.3390/cells11010126

Cited by 13 publications

(8 citation statements)

References 158 publications

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“…It is a ubiquitous transmembrane glycoprotein which acts as a receptor and regulates several interactions between cells and the extracellular matrix. Its isoforms are predominantly overexpressed in inflammation and cancer [ 22 , 226 ]. HA presents high affinity for CD44, in addition to pH-responsiveness.…”

Section: Resultsmentioning

confidence: 99%

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

Garbati,

Picco,

Magrassi

et al. 2024

Pharmaceutics

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The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical–chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

Garbati,

Picco,

Magrassi

et al. 2024

Pharmaceutics

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“…However, in non-injured and sham-operated groups, 4-MU treatment influenced bacterial intragroup composition. In particular, the reduced variability observed in samples obtained from non-injured animals, after 4-MU treatment, underlines the relevance of HA in maintaining gut bacteria homeostasis in normal conditions [ 52 ]. HA may also influence commensal bacterial variability after laparotomy, as suggested by the ability of 4-MU to restore α-diversity indexes in the sham-operated group.…”

Section: Discussionmentioning

confidence: 99%

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

Bosi

Banfi

Bistoletti

et al. 2022

Cells

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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.

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“…The gastrointestinal tract (GIT) hosts a pool of immune cells representing 70% of the entire immune system, and the largest population of macrophages in the human body [279]. Through its local immune system, the GIT detects and responds to the local microbiome [263], but also impacts upon remote immune processes [280][281][282][283][284][285][286][287][288][289][290][291][292][293][294][295]. During the past years multiple experimental studies have revealed that the microbiome and local immune system of the GIT may modulate distant inflammation within the cardiovascular system and brain [242,245,262,263,272,274,278,279,[296][297][298][299][300][301][302].…”

Section: Immune Impact and Therapeutic Perspectives Of The Intestinal...mentioning

confidence: 99%

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Poller¹,

Heidecker²,

Ammirati³

et al. 2022

Preprint

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During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

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Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis

Cited by 13 publications

References 158 publications

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

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

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

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