Patologías funcionales post-infecciosas: epidemiología, factores de riesgo y tratamiento / Post-infectious functional gastrointestinal disorders: epidemiology, risk factors and treatment

Infectious gastroenteritis is a risk factor for developing post-infectious functional gastrointestinal disorders (PI-FGDs), mainly irritable bowel syndrome (IBS) and functional dyspepsia (FD). It is a significant subgroup of patients due to frequent episodes of gastrointestinal infections. Symptoms in PI-FGD patients can prevail for more than twelve months, especially if infective agents are bacteria or parasites. Symptoms are indistinguishable from their non-infective equivalents (IBS and FD). Risk factors for developing PI-FGD are: female gender, type and severity of the gastrointestinal infection, high anxiety levels and younger age. Main pathogenic mechanisms are alteration of permeability and immunity. Mucosa inflammation prevails only at early stage; however, with follow-up it can be reduced or normalized. Nevertheless, certain alterations prevail, such as hypersensitivity. These events are treated in the same way as IBS or FD.

La gastroenteritis infecciosa es un factor de riesgo para desarrollar un trastorno digestivo funcional postinfeccioso (TDF-PI), principalmente síndrome de intestino irritable (SII) y dispepsia funcional (DF). Es un subgrupo de pacientes relevante debido a lo frecuente que son las infecciones gastrointestinales. Los síntomas en los pacientes con TDF-PI se pueden prolongar por más de un año, especialmente cuando los agentes infecciosos son bacterias o parásitos. Los síntomas son indistinguibles con respecto a los de sus equivalentes no infecciosos (SII y DF). Los factores de riesgo para desarrollar TDF-PI son el sexo femenino, el tipo y la severidad de la infección gastrointestinal, los niveles altos de ansiedad, y la menor edad. Los principales mecanismos patogénicos son la alteración de la permeabilidad y de inmunidad. La inflamación de la mucosa predomina solo al principio pero con el seguimiento esta disminuye o se normaliza, a pesar de lo cual ciertas alteraciones como la hiperensibilidad permanecen. Estos cuadros se tratan de la misma manera que un SII o DF.

Electroacupuncture of "Tianshu" (ST 25) Suppresses Visceral Pain Possibly by Down-regulating Mast Cell Activation, and Tryptase and SP Expression in Rats with Post-infectious Irritable Bowel Syndrome / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) on visceral pain and colonic mast cell (MCs) number and tryptase and SP expression in post-infectious irritable bowel syndrome (PI-IBS) rats, so as to reveal its mechanisms underlying improvement of PI-IBS. METHODS: Forty-five female Wistar rats were randomly divided into control, model and EA groups (15 rats/ group, 3 rats/group used for H. E. staining, and 12 rats/group for immunohistochemistry). The PI-IBS model was established by intra-anal injection of mixed liquor of 50% ethyl alcohol and trinitro-benzene-sulfonic acid (TNBS). EA (2 Hz/15 Hz, 0.5-1.0 mA) was applied to bilateral "Tianshu" (ST 25) for 30 min, once every day for 14 days. The visceral pain was measured by abdominal withdrawal reflex (AWR), for which the rectal implanted air balloon was dilated by infusion of normal saline. The histopathological changes of the colon tissue were observed after H. E. staining, and the colonic MCs were displayed by Toluidine blue staining. The expression of tryptase and SP proteins in the colon specimens were detected by immunohistochemistry. RESULTS: The AWR threshold was significantly lowered in the model group relevant to the control group (P<0.05) and considerably increased after EA intervention in comparison with the model group (P<0.05). The number of MCs and the expression levels of colonic tryptase and SP proteins in the colon tissues were significantly higher in the model group than in the control group (P<0.05), and obviously lower after EA intervention in the EA group than in the model group (P<0.05). CONCLUSION: EA of "Tianshu" (ST 25) can inhibit visceral pain in PI-IBS rats, which may be associated with its effects in activating MCs and down-regulating the expression of tryptase and SP proteins in the colonic tissues.

Dynamic Changes of IL-17, occludin, and ZO-1 in Mice with Post-infectious Irritable Bowel Syndrome / 中山大学学报(医学科学版)

[Objective] To observe the dynamic changes of intestinal IL-17,occludin,and ZO-1 in mice with postinfectious irritable bowel syndrome (PI-IBS).[Methods] Forty C57BL/6 mice were randomly divided into 5 groups:control group and infection groups (2 weeks,4 weeks,6 weeks,and 8 weeks after trichinella infection).Infection groups were given by gavaging of 400～500 Trichinella spiralis in 0.2 mL of normal saline.The body weight of mice were recorded at week 2,4,6,and 8 after infection.The visceral sensitivity of mice was measured by the abdominal withdrawal reflex (AWR).The stool was collected continuously for 8 hours to calculate the percentage of fecal water content.Pathological changes of gut were observed by HE staining.The expressions of IL-17,occludin,and ZO-1 in ileocecus and colon were detected by immunohistochemistry and Western blotting.[Results] At week 2 after infection,the acute inflammation of the intestinal tract was observed and the body weight of mice were significantly decreased (P=0.000).Until week 8 after infection,the intestinal inflammation and body weight of mice recovered to normal.When the colorectal dilatation capacity was 0.35 and 0.5 mL,the AWR scores in the infection groups were significantly higher than those in the control group (P＜0.01).The percentages of fecal water content in the infection groups were significantly higher than those in the control group (P＜0.05).Compared with the control group,the expressions of IL-17 were significantly decreased in week 2 group (P＜0.05) and increased in week 8 group (P＜0.05).The expressions of occludin and ZO-1 in the infection groups were significantly lower than those in the control group (P＜0.05).[Conclusion] The dynamic changes of IL-17 and the decrease of Tight junction proteins may be one of the mechanisms of visceral hypersensitivity and increased percentages of fecal water content.They may be involved in the development of PI-IBS.

Study on phenotype and function of intestinal gamma delta T lymphocytes in mice with post-infectious irritable bowel syndrome / 中国免疫学杂志

Objective:To investigate the phenotype and function of the intestinal γδT lymphocytes in post-infectious irritable bowel syndrome mouse model. Methods:The mouse model for post-infectious irritable bowel syndrome was established by the infection with trichinella spiralis. The intestinal inflammation,abdominal withdrawal reflex( AWR) and colon transportation test were observed. 2 and 8 weeks later,the animals were sacrificed and the lymphocytes in the intestinal lymph nodes and spleen were collected,from which the γδT lymphocytes were isolated and purified by monoclonal antibody-immuno-microbeads method. The functions of the purified γδT lymphocytes were evaluated,including proliferation by 3 HTdR;CD69,CD62L molecule staining by flow cytometry. Furthermore,the con-centration of cytokine IL-17 and IFN-γ in the supernatant of the cultured γδT lymphocytes were detected by ELISA. Results: At 2nd weeks after infection,significant intestinal inflammation was observed,with increasingγδT lymphocytes,proliferating and activating with increasing production of IL-17. At 8th weeks after infection, the intestinal inflammation disappeared, whereas the number of γδT lymphocytes remained increasing,also with proliferating and activating with increasing production of IL-17. Meanwhile,the mice show higher AWR score and Bristol score. Conclusion: γδT lymphocytes could participate in the pathogenesis of PI-IBS via their proliferation,activation and production of IL-17.

Effects of Volatile Oil of Pogostemon cablin on the Expression of Tight Junction Protein ZO-1 and Occlu-din in Colonic Mucosal Epithelial Cells of Rats with Post-infectious Irritable Bowel Syndrome / 中国药房

OBJECTIVE:To study the effects of volatile oil of Pogostemon cablin on the expression of tight junction proteins ZO-1 and Occludin in colonic mucosal epithelial cells of rats with post-infectious irritable bowel syndrome(PI-IBS). METHODS:Rats were randomly divided into normal control group(distilled water),model group(distilled water),Trimebutine maleate tablet group(TMT,0.1 g/kg)and volatile oil of P. cablin low-dose,medium-dose and high-dose groups [2,3,4 g(crude drug)/kg] with 8 rats in each group. Except for normal control group,those groups were given colon perfusion of acetic acid to induce PI-IBS mod-el. After modeling,they were given relevant medicine intragastrically once a day for consecutive 5 days. The expression of ZO-1 and Occludin [by IOD] and their distribution were detected by immunohistochemistry. RESULTS:In normal control group,ZO-1 and Occludin evenly distributed on the top of enterocyte,manifesting as alveolate and punctiform;in model group,ZO-1 and Oc-cludin scattered on the top of enterocyte,showing uneven dyeing or fade;the distribution of ZO-1 and Occludin in volatile oil of P. cablin groups was similar to normal control group,and its dyeing was lighter than that of normal control group. IOD value of ZO-1 and Occludin in model group were lower than in normal control group(P<0.01);those of volatile oil of P. cablin high-dose group and the IOD value of ZO-1 of P. cablin medium-dose group and TMT group were higher than those of model group (P<0.05 or P<0.01). CONCLUSIONS:The volatile oil of P. cablin can up-regulate the expression of tight junction proteins ZO-1 and Occlu-din in colonic mucosal epithelial cells of rats with PI-IBS.

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model

Objective: To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. Methods: Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. Results: Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05). Conclusions: Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model

OBJECTIVE@#To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model.@*METHODS@#Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.@*RESULTS@#Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05).@*CONCLUSIONS@#Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.

Role of gut pathogens in development of irritable bowel syndrome.

Acute infectious gastroenteritis is one of the most commonly identifiable risk factors for the development of irritable bowel syndrome (IBS). A number of bacterial, viral and parasitic pathogens have been found to be associated with the development of IBS and other functional gastrointestinal (GI) disorders. Epidemiological studies have identified demographic and acute enteritis-related risk factors for the development of post-infectious-IBS (PI-IBS). Immune dysregulation, alterations in barrier function, serotonergic and mast cell activation have been identified as potential pathophysiological mechanisms. Additionally, variations in host genes involved in barrier function, antigen presentation and cytokine response have been associated with PI-IBS development. However, it is unknown whether specific pathogens have unique effects on long-term alterations in gut physiology or different pathogens converge to cause common alterations resulting in similar phenotype. The role of microbial virulence and pathogenicity factors in development of PI-IBS is also largely unknown. Additionally, alterations in host gut sensation, motility, secretion, and barrier function in PI-IBS need to be elucidated. Finally, both GI infections and antibiotics used to treat these infections can cause long-term alterations in host commensal microbiota. It is plausible that alteration in the commensal microbiome persists in a subset of patients predisposing them to develop PI-IBS.

Changes of electric activity of mesenteric nerve in guinea pig model with post-infectious irritable bowel syndrome / 中华消化杂志

Objective To investigate the changes of spontaneous activity of mesenteric nerve in guinea pig model with post-infectious irritable bowel syndrome (PI-IBS)and the response of mesenteric nerve to pressure and acid stimulation in order to clarify whether mesenteric nerve involves in the pathogenesis of the PI-IBS.Methods A total of 20 female adult guinea pigs were divided into PI-IBS group and control group,ten in each group.Guinea pigs of PI-IBS group were gastric lavaged with 8 000 to 10 000 Trichinella spiralis larves at a time,and were fed for six to eight weeks to establish PI-IBS model.The sample of proximal jejunum was taken and mesenteric nerves of guinea pigs of both groups were isolated.Spontaneous activity of mesenteric nerve was recorded in PI-IBS and control groups by extracellular electrophysiological recorder.The changes of mesenteric nerve activity were recorded after the intestine of two groups was stimulated with different dilation pressure (5 ,10,20 and 30 cmH2 O, 1 cmH2 O=0.098 kPa)and different concentration of hydrochloric acid (HCl)solution (1 ,10,20 and 30 mmol/L).Unpaired t test was performed for the comparison between the two groups.Results The spontaneous discharge frequency of mesenteric nerve of PI-IBS group was (75 .98±14.01)Hz,while that of control group was (31 .36±4.71)Hz,which was,obviously lower than that of PI-IBS group (t =9.55 ,P <0.01).After the intestine of PI-IBS group was dilated with 5 ,10,20 and 30 cmH2 O pressure, the discharge frequency of mesenteric nerve increased by (36.21±12.41)Hz,(40.18±10.48)Hz,(45.72± 10.11)Hz,and (56.05 ±9.27)Hz than baseline,respectively;likewise,in control group,after dilated with same pressure,the discharge frequency increased by (20.00±5.28)Hz,(22.13 ±3.34)Hz,(28.55 ± 4.80)Hz and (35 .07±7.56)Hz than baseline,respectively,which were significantly lower than those of PI-IBS group (t=3.80,3.19,4.85 and 5 .55 ,P =0.028,0.006,0.009 and 0.003).After the intestin of PI-IBS group was stimulated with 1 ,10,20 and 30 mmol/L HCl,the discharge frequency of mesenteric nerve increased by (2.10±0.89 )Hz,(10.87 ±3.30 )Hz,(19.59 ±2.99 )Hz and (34.49 ±6.80)Hz after stimulation respectively,while in control group after stimulated with same concentrations of HCl, the discharge frequency increased by (0.26 ±0.21 )Hz,(5 .55 ±3.91 )Hz,(7.70 ±2.53)Hz,(14.90± 10.10)Hz,respectively,which were significantly lower than those of PI-IBS group (t=6.36,3.29,9.60 and 5.09;P =0.002,0.049,<0.01 and 0.005).Conclusion The spontaneous electric activity of mesenteric nerve of PI-IBS guinea pig model increased and was more sensitive to pressure and acid,which indicated that hypersensitivity of mesenteric nerve might play an important role in the pathogenesis of PI-IBS.

Síndrome do intestino irritável pós-infecção intestinal / Irritable bowel syndrome after intestinal infection

A síndrome do intestino irritável (SII) é um distúrbio funcional do trato gastrointestinal, caracterizado por dor abdominal e alterações do hábito intestinal, não explicadas por anormalidades bioquímicas ou orgânicas. Embora a maioria dos pacientes relate início insidioso dos sintomas, em um subgrupo eles aparecem após episódio de gastroenterite aguda, denominada SII pós-infecciosa (SII-PI). Os agentes infecciosos envolvidos incluem vírus, parasitas e bactérias patogênicas. O tratamento da SII-PI é semelhante ao da SII idiopática. Antibióticos e probióticos são terapias promissoras

Irritable bowel syndrome (IBS) is a funcional gastrointestinal disorder characterized by abdominal pain and changes in bowel habits, not explained by any organic or biochemical abnormalities. Although most patients describe an insidious onset of symptoms, a subgroup of individuals describes the onset of IBS symptoms following an episode of acute gastroenteritis, know as post-infectious IBS (PI-IBS). The infectious agents involved in the development of PI-IBS include pathogenic bacteria, parasites and viruses. Treatment of PI-IBS is similar to that idiopathic IBS. Antibiotics and probiotics appear to represent promising therapies in PI-IBS

Increased Immunoendocrine Cells in Intestinal Mucosa of Postinfectious Irritable Bowel Syndrome Patients 3 Years after Acute Shigella Infection: An Observation in a Small Case Control Study

PURPOSE: Postinfectiously irritable bowel syndrome (PI-IBS) develops in 3-30% of individuals with bacterial gastroenteritis. Recent studies demonstrated increases in inflammatory components in gut mucosa of PI-IBS patients even after complete resolution of infection. We aimed to investigate histological changes in colon and rectum of PI-IBS subjects after long term period of infection. MATERIALS AND METHODS: We recruited PI-IBS subjects who had been diagnosed IBS after complete resolution of enteritis caused by shigellosis outbreak 3 years earlier. We compared unmatched four groups, PI-IBS (n = 4), non PI-IBS (n = 7), D-IBS (n = 7, diarrhea predominant type) and healthy controls (n = 10). All of them underwent colonoscopic biopsy at three areas, including descending colon (DC), sigmoid colon (SC) and rectum, which were assessed for 5-hydroxytryptamine (5-HT)/peptide YY (PYY)-containing enterochromaffin (EC) cell, intraepithelial (IEL) and lamina propria T lymphocyte (CD3), CD8 lymphocytes, mast cells and CD68/calprotectin+ macrophages. RESULTS: All subjects had no structural or gross abnormalities at colonoscopy. In PI-IBS, 5-HT containing EC cells, PYY containing EC cells, IELs, CD3 lymphocytes, CD8 lymphocytes, mast cells, and CD68 + macrophages were increased compared to control (p < 0.05). In D-IBS, PYY containing EC cells, IELs, and CD3 lymphocytes were increased compared to control (p < 0.05). In PI-IBS, 5-HT containing EC cells tended to increase and PYY containing EC cells, CD8 lymphocytes, mast cells, and CD68+ macrophages were increased compared to non PI-IBS (p < 0.05). Calprotectin + marcrophages were decreased in PI-IBS, non PI-IBS and IBS compared to control. CONCLUSION: The immunoendocrine cells were sporadically increased in PI-IBS, non PI-IBS and D-IBS compared with control. Our findings in a very small number of patients suggest that mucosal inflammation may play a role in long-term PI-IBS, and that other sub-groups of IBS and larger scale studies are needed to confirm this observation.

Ultrastructure of colonic mucosa in post infectious irritable bowel syndrome / 中华消化内镜杂志

se,instead of simply a functional disease,wtth biochemical basis.

The Development of Irritable Bowel Syndrome after Shigella Infection: 3 Year Follow-up Study / 대한소화기학회지

BACKGROUND AND AIMS: Bacterial gastroenteritis seems to be a risk factor of irritable bowel syndrome (IBS). The incidence of post-infectious IBS (PI-IBS) was reported to be in the range of 7-31%, but few studies have reported long term follow-up results. So, we investigated the clinical course and prognosis of PI-IBS three years after shigella infection. METHODS: The subjects were recruited from our previous study, in which we investigated the incidence and risk factors of PI-IBS. We had a questionnaire based on interview with 120 controls and 124 patients who had shigella infection three years ago. Both groups were evaluated for the presence of IBS, functional bowel disorders (FBD) except IBS before, one and three years after the infection, respectively. RESULTS: Ninty-five patients (76.6%) and 105 controls (87.5%) completed the questionnare. In patients group, 7 cases had IBS prior to infection (previous IBS), 12 cases (13.8%) had IBS after 1 year (PI-IBS). Four cases developed IBS newly after 3 years (new IBS). Thirteen cases (14.9%) in patients and 4 cases (4.5%) in controls had IBS over 3 years (OR 3.93: 1.20-12.86). The recovery rate over 3 years were 50.0% (2/4) in previous IBS and 25% (3/12) in PI-IBS. The incidence of PI-IBS after 3 years in previous FBD subjects was 28.6% and was 10.6% in normals (p<0.05). The female gender was a risk factor for FBD. CONCLUSIONS: Bacterial gastroenteritis is a trigger factor of IBS. About a quarter of PI-IBS patients are recovered over 3 years. Previous FBD except IBS is a risk factor after 3 years.

Discussion on Chinese medicine in treating post-infectious irritable bowel syndrome / 中华中医药杂志

The pathogenesis of post- infectious irritable bowel syndrome(PI-IBS)involves abnormal intestinal immune barrier, which possibly includes the pathological aspects: Intestinal and systemic changes in T lymphocyte; the change of inflammatory cytokines; a increase in intestinal mast cells and enterochromaffin cells and so on. Treatment by western medicine based largely on symptomatic treatment. TCM thinks that the fundamental organ of the irritable bowel syndrome is the liver. Emotional factors inducing liver dysfunction lead to the symptoms of irritable bowel syndrome. The pathogenesis of IBS is, the disorder of movement of qi in liver and spleen. Stagnation of liver-QI with deficiency of the spleen or disharmony between liver and spleen is the key pathogenesis of post-infectious irritable bowel syndrome. On this basis, in various stages of the disease, there may be a different pathogenesis. As a special type of IBS, the balance of vital qi and evil factors determine the disease progression of PI-IBS, in the treatment course also should not forget dispelling pathogenic factors while strengthening body resistance, tonifying deficiency and removing dampness。