scholarly journals Microbiota-neuroimmune cross talk in stress-induced visceral hypersensitivity of the bowel

2020 ◽  
Vol 318 (6) ◽  
pp. G1034-G1041
Author(s):  
Isabelle A. M. van Thiel ◽  
Wouter J. de Jonge ◽  
Isaac M. Chiu ◽  
Rene M. van den Wijngaard
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Cross Talk ◽  
Visceral Pain ◽  
Current Knowledge ◽  
Visceral Hypersensitivity ◽  
Pain Sensation ◽  
Colorectal Distension ◽  
Irritable Bowel ◽  
Review Current

Visceral hypersensitivity of the lower gastrointestinal tract, defined as an increased response to colorectal distension, frequently prompts episodes of debilitating abdominal pain in irritable bowel syndrome (IBS). Although the pathophysiology of IBS is not yet fully elucidated, it is well known that stress is a major risk factor for development and acts as a trigger of pain sensation. Stress modulates both immune responses as well as the gut microbiota and vice versa. Additionally, either microbes themselves or through involvement of the immune system, activate or sensitize afferent nociceptors. In this paper, we review current knowledge on the influence of stress along the gut-brain-microbiota axis and exemplify relevant neuroimmune cross talk mechanisms in visceral hypersensitivity, working toward understanding how gut microbiota-neuroimmune cross talk contributes to visceral pain sensation in IBS patients.

scholarly journals Food Additives, Gut Microbiota, and Irritable Bowel Syndrome: A Hidden Track

2020 ◽  
Vol 17 (23) ◽  
pp. 8816
Author(s):  
Emanuele Rinninella ◽  
Marco Cintoni ◽  
Pauline Raoul ◽  
Antonio Gasbarrini ◽  
Maria Cristina Mele
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Visceral Pain ◽  
Current Knowledge ◽  
Food Additives ◽  
Modern Human ◽  
Low Grade ◽  
Irritable Bowel ◽  
Few Data ◽  
The Impact

The interactions between diet, gut microbiota, and irritable bowel syndrome (IBS) have many complex mechanisms that are not fully understood. Food additives are one component of the modern human diet that deserves attention from science and government policies. This review aims at identifying the current knowledge about the impact of food additives on gut microbiota and their potential role in the development of IBS. To date, few data on the effect of food additives on gut microbiota in IBS patients are available. However, exposure to food additives could induce the dysbiosis and dysregulation of gut homeostasis with an alteration of the gut barrier and activation of the immune response. These microbial changes could exacerbate the gut symptoms associated with IBS, such as visceral pain, low-grade inflammation, and changes in bowel habits. Some additives (polyols) are excluded in the low fermentable oligo-, di- and monosaccharide, and polyol (FODMAP), diets for IBS patients. Even if most studies have been performed in animals, and human studies are required, many artificial sweeteners, emulsifiers, and food colorants could represent a potential hidden driver of IBS, through gut microbiota alterations. Consequently, food additives should be preventively avoided in the diet as well as dietary supplements for patients with IBS.

scholarly journals Small-Conductance Ca2+-Activated K+ Channels 2 in the Hypothalamic Paraventricular Nucleus Precipitates Visceral Hypersensitivity Induced by Neonatal Colorectal Distension in Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning-Ning Ji ◽  
Lei Du ◽  
Ying Wang ◽  
Ke Wu ◽  
Zi-Yang Chen ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Protein Transport ◽  
Visceral Pain ◽  
Neuronal Firing ◽  
Visceral Hypersensitivity ◽  
Hypothalamic Paraventricular Nucleus ◽  
Colorectal Distension ◽  
The Central Nervous System ◽  
Irritable Bowel ◽  
Small Conductance

Visceral hypersensitivity is one of the pivotal pathophysiological features of visceral pain in irritable bowel syndrome (IBS). Small-conductance Ca2+-activated K+ channel (SK) is critical for a variety of functions in the central nervous system (CNS), nonetheless, whether it is involved in the pathogenesis of visceral hypersensitivity remain elusive. In this study, we examined mechanism of SK2 in hypothalamic paraventricular nucleus (PVN) in the pathogenesis of visceral hypersensitivity induced by neonatal colorectal distension (CRD). Rats undergoing neonatal CRD presented with visceral hypersensitivity as well as downregulated membrane SK2 channel and p-PKA. Intra-PVN administration of either the membrane protein transport inhibitor dynasore or the SK2 activator 1-EBIO upregulated the expression of membrane SK2 in PVN and mitigated visceral hypersensitivity. In addition, 1-EBIO administration reversed the increase in neuronal firing rates in PVN in rats undergoing neonatal CRD. On the contrary, intra-PVN administration of either the SK2 inhibitor apamin or PKA activator 8-Br-cAMP exacerbated the visceral hypersensitivity. Taken together, these findings demonstrated that visceral hypersensitivity is related to the downregulation of membrane SK2 in PVN, which may be attributed to the activation of PKA; pharmacologic activation of SK2 alleviated visceral hypersensitivity, which brings prospect of SK2 activators as a new intervention for visceral pain.

scholarly journals P2X3 Receptor in Primary Afferent Neurons Mediates the Relief of Visceral Hypersensitivity by Electroacupuncture in an Irritable Bowel Syndrome Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fang Zhang ◽  
Zhe Ma ◽  
Zhijun Weng ◽  
Min Zhao ◽  
Handan Zheng ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Receptor Protein ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Expression Levels ◽  
Behavioral Studies ◽  
Irritable Bowel

Background. Electroacupuncture (EA) has been confirmed effectiveness in the treatment of irritable bowel syndrome (IBS), and P2X3 receptors in the peripheral and central neurons participate in the acupuncture-mediated relief of the visceral pain in IBS. Objective. To reveal the neurobiological mechanism that P2X3 receptor of colonic primary sensory neurons in the dorsal root ganglia of the lumbosacral segment is involved in the alleviation of visceral hypersensitivity by EA in an IBS rat model. Methods. The IBS chronic visceral pain rat model was established according to the method of Al-Chaer et al. EA at the bilateral He-Mu points, including ST25 and ST37, was conducted for intervention. The behavioral studies, histopathology of colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction assays were used to observe the role of P2X3 receptor in the colon and related DRG in relieving visceral hypersensitivity by EA. Results. EA significantly reduced the behavior scores of the IBS rats under different levels (20, 40, 60, 80 mmHg) of colorectal distention stimulation and downregulated the expression levels of P2X3 receptor protein and mRNA in colon and related DRG of the IBS rats. EA also regulated the electrical properties of the membranes, including the resting membrane potential, rheobase, and action potential of colon-associated DRG neurons in the IBS rats. Conclusion. EA can regulate the P2X3 receptor protein and mRNA expression levels in the colon and related DRG of IBS rats with visceral pain and then regulate the excitatory properties of DRG neurons.

scholarly journals Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
L. D. Wang ◽  
J. M. Zhao ◽  
R. J. Huang ◽  
L. Y. Tan ◽  
Z. H. Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Regulatory Function ◽  
Visceral Hyperalgesia ◽  
Spinal Dorsal ◽  
Dorsal Horns ◽  
Irritable Bowel

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCεprotein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCεin the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCεin spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCεof spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome

2012 ◽  
Vol 303 (2) ◽  
pp. G141-G154 ◽  
Author(s):  
D. Keszthelyi ◽  
F. J. Troost ◽  
A. A. Masclee
Keyword(s):  
Irritable Bowel Syndrome ◽  
Brain Imaging ◽  
Visceral Pain ◽  
Gastrointestinal Disorder ◽  
Visceral Hypersensitivity ◽  
Visceral Perception ◽  
Optimal Method ◽  
Flexor Reflex ◽  
Sensory Stimuli ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a “biological hallmark” for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms “assessment of visceral pain/visceral nociception/visceral hypersensitivity” and “irritable bowel syndrome.” Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

scholarly journals Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-life Adversity

2020 ◽  
Author(s):  
Enqi Wu ◽  
Song Jingzhu ◽  
Pei Lingpeng ◽  
Ling Yaqin
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Maternal Separation ◽  
Visceral Hypersensitivity ◽  
Early Adversity ◽  
Early Life Adversity ◽  
Rat Models ◽  
Fecal Water ◽  
Irritable Bowel

Abstract Background: The aims of this study was to identify the effect of modeling procedures on bacterial communities and investigate whether different modeling procedures lead to consistent patterns of gut microbiota compositions. Methods: Two IBS rat models (MS alone and multiple-early-adversity modeling) were established and the gut microbiotas were analyzed using 16S-rRNA-based high-throughput sequencing methods. Results: Rats from both models exhibited visceral hypersensitivity and the two model groups exhibited differences in the extent of visceral sensitivity and fecal water content. The microbial community structure of the two models exhibited significant differences compared to the controls, while the two model groups also exhibited significant differences between them. Furthermore, microbial community functional predictions suggested that the two models exhibited different abundances of metabolisms and pathways. Several common and distinct characteristic differences were also observed between the two model groups. Alloprevotella were more abundant in both model groups, while Butyricicoccus, Turicibacter, Ruminococcus, and Clostridium_sensu_stricto along with the family it belongs to were less abundant relative to controls. In addition, the abundance of Clostridium_IV, Corynebacterium, Rothia, Elusimicrobium, Romboutsia, Allobaculum, Parasutterella and their related taxa were specifically associated with MS group, whereas Butyricimonas and Vampirovibrio along with its related taxa were specifically associated with MAM group. Among those, Butyricimonas, Butyricicoccus and Corynebacterium were found partially mediates early adversity exposure-induced visceral hypersensitivity. Conclusions: our results highlight the importance in evaluating gut microbiota characteristics in IBS research while also systematically considering potential modeling procedural differences. The microbial compositional/functional differences identified in this study were suggestive to further investigation of mechanism of early adversity induced IBS.

Electroacupuncture Relieves Irritable Bowel Syndrome by Regulating IL-18 and Gut Microbial Dysbiosis in a Trinitrobenzene Sulfonic Acid-Induced Post-Inflammatory Animal Model

2020 ◽  
Vol 48 (01) ◽  
pp. 77-90 ◽  
Author(s):  
Ya-Fang Song ◽  
Li-Xia Pei ◽  
Lu Chen ◽  
Hao Geng ◽  
Meng-Qian Yuan ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Sulfonic Acid ◽  
Visceral Pain ◽  
Fecal Microbiota ◽  
Visceral Hypersensitivity ◽  
Trinitrobenzene Sulfonic Acid ◽  
Model Group ◽  
Microbial Dysbiosis ◽  
Colorectal Distention ◽  
Irritable Bowel

Post inflammatory irritable bowel syndrome (PI-IBS), a subset of IBS, is characterized by symptoms of visceral pain, bloating, and changed bowel habits that occur post initial episode of intestinal infection. Gut microbial dysbiosis or inflammation plays a key role in the pathogenesis of abdominal hypersensitivity of PI-IBS. Electroacupuncture (EA) stimulation results in an alleviated PI-IBS-associated symptom. This study investigated the effect of EA on IL-18 and gut microbial dysbiosis in one visceral hypersensitive rat models with PI-IBS. A trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity rat model was developed. EA stimulation was applied to the ST25 and ST36 acupoints. Animals were assessed using abdominal withdrawal reflex (AWR) scores to determine the development of colonic visceral hypersensitivity. The 16S rRNA was used to correlate microbial diversity. IL-18 expression in colon was quantified by quantitative real-time PCR and western blotting. We identified that model rats had an increased visceral hypersensitivity to colorectal distention at different distention pressures compared with the normal group. Sensitivity to colorectal distention decreased after EA stimulation. The composition of the fecal microbiota was different between groups. Specifically, in the model group Empedobacter, Psychrobacter, Enterococcus, Butyricimonas, Vampirovibrio, Kurthia, Intestinimonas, Neisseria, Falsiporphyromonas, Bilophila, Fusobacterium, Alistipes, Veillonella, Flavonifractor, Clostridium XlVa were more abundant affected genera, whereas Lactobacillus was enriched in normal rats. EA stimulation was correlated with significant decrease in the phyla of Fusobacteria. The mRNA and protein levels of IL-18 were higher in the model group. Meanwhile, EA stimulation attenuated this response. In a word, our findings suggest that PI-IBS is associated with significant increase in IL-18 levels as well as an alteration in microbiome diversity. These changes can be reversed with EA treatment. EA stimulation has a positive effect in alleviating symptoms of visceral hypersensitivity and protecting the gastrointestinal tract.

scholarly journals Targeting spinal TRAF6 expression attenuates chronic visceral pain in adult rats with neonatal colonic inflammation

2020 ◽  
Vol 16 ◽  
pp. 174480692091805 ◽  
Author(s):  
Rui-Xia Weng ◽  
Wei Chen ◽  
Jia-Ni Tang ◽  
Qian Sun ◽  
Meng Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Colonic Inflammation ◽  
Spinal Dorsal ◽  
Irritable Bowel

Background Irritable bowel syndrome is one of the most common gastrointestinal disorders. It is featured by abdominal pain in conjunction with altered bowel habits. However, the pathophysiology of the syndrome remains largely unknown. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be involved in neuropathic pain. The aim of this study was to investigate roles and mechanisms of TRAF6 in the chronic visceral hypersensitivity. Methods Visceral hypersensitivity was induced by neonatal colonic inflammation and was identified by colorectal distention. The protein level, RNA level, and cellular distribution of TRAF6 and its related molecules were detected with Western blot, quantitative polymerase chain reaction, and immunofluorescence. In vitro spinal cord slice recording technique was performed to determine the synaptic transmission activities. Results Neonatal colonic inflammation rats displayed visceral hypersensitivity at the age of six weeks. The expression of TRAF6 was obviously upregulated in spinal cord dorsal horn of neonatal colonic inflammation rats at the age of six weeks. Immunofluorescence study showed that TRAF6 was dominantly expressed in spinal astrocytes. Intrathecal injection of TRAF6 small interfering RNA (siRNA) significantly reduced the amplitude of spontaneous excitatory postsynaptic currents at the spinal dorsal horn level. Furthermore, knockdown of TRAF6 led to a significant downregulation of cystathionine β synthetase expression in the spinal dorsal horn of neonatal colonic inflammation rats. Importantly, intrathecal injection of TRAF6 siRNA remarkably alleviated visceral hypersensitivity of neonatal colonic inflammation rats. Conclusions Our results suggested that the upregulation of TRAF6 contributed to visceral pain hypersensitivity, which is likely mediated by regulating cystathionine β synthetase expression in the spinal dorsal horn. Our findings suggest that TRAF6 might act as a potential target for the treatment of chronic visceral pain in irritable bowel syndrome patients.

scholarly journals Modulation of visceral sensitivity by faecal microbiota transplantation (FMT): the active role of gut microbiota in the persistence of abdominal pain

2020 ◽  
Author(s):  
Elena Lucarini ◽  
Vincenzo Di Pilato ◽  
Carmen Parisio ◽  
Laura Micheli ◽  
Alessandra Toti ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Gut Microbiota ◽  
Visceral Pain ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Active Role ◽  
Visceral Hypersensitivity ◽  
Faecal Microbiota ◽  
Healthy Donors ◽  
Composition And Structure

Abstract Background. Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing the persistence of visceral hypersensitivity consequent to colitis induced by the intra-rectal injection of 2,4-dinitrobezenesulfonic acid (DNBS) in rats. Results: The effect of faecal microbiota transfer (FMT) from viscerally hypersensitive DNBS and naïve donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. FMT from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition and structure of the gut microbiota at phylum (Proteobacteria and Firmicutes to Bacteroides ratio) and family levels (Enterobacteriaceae, Akkermansiaceae and Lachnospiraceae). Acetic acid was significantly increased in the recipients FMT from DNBS donors. Gut cytokine profile, as well as tryptophan metabolism were similarly altered after FMT from both DNBS and naïve donors. By contrast, no significant alterations of colon histology, permeability and monoamines levels were detected. Finally, following FMT from healthy donors to DNBS-treated animals, a counteraction of persistent visceral pain was achieved. Conclusions: The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota modulation on persistent abdominal pain.

scholarly journals Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome

2016 ◽  
Vol 311 (5) ◽  
pp. G934-G941 ◽  
Author(s):  
Dervla O'Malley
Keyword(s):  
Irritable Bowel Syndrome ◽  
Cross Talk ◽  
Visceral Pain ◽  
Recurrent Abdominal Pain ◽  
Colonic Transit ◽  
Bowel Habit ◽  
Signaling Axis ◽  
Increased Sensitivity ◽  
Irritable Bowel ◽  
Dysfunctional Communication

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain, bloating, and disturbed bowel habit, symptoms that impact the quality of life of sufferers. The pathophysiological changes underlying this multifactorial condition are complex and include increased sensitivity to luminal and mucosal factors, resulting in altered colonic transit and visceral pain. Moreover, dysfunctional communication in the bidirectional signaling axis between the brain and the gut, which involves efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones, and local paracrine and neurocrine factors, including immune and perhaps even microbial signaling molecules, has a role to play in this disorder. This minireview will examine recent advances in our understanding of the pathophysiology of IBS and assess how cross talk between hormones, immune, and microbe-derived factors and their neuromodulatory effects on peripheral nerves may underlie IBS symptomatology.

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