ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blind...     

Diagnosis of small intestinal bacterial overgrowth: the challenges persist!

Small intestinal bacterial overgrowth was originally defined in the context of an overt malabsorption syndrome and diagnostic tests were developed and validated accordingly. More recently, the concept of intestinal contamination with excessive numbers of bacteria, especially those of colonic type, has been extended beyond the bounds of frank maldigestion and malabsorption to explain symptomatology in disorders as diverse as irritable bowel syndrome, celiac sprue and nonalcoholic fatty liver disease. Owing to a lack of consensus with regard to the optimal diagnostic criteria (the ‘gold standard’) for the diagnosis of bacterial overgrowth, the status of these new concepts is unclear. This review sets out to critically appraise the various diagnostic approaches that have been taken and are currently employed to diagnose small intestinal bacterial overgrowth.     

Diagnosis and pharmacological management of small intestinal bacterial overgrowth in children with intestinal failure

The present article provides a general overview of the possible diagnostic procedures available for the management of small intestinal bacterial overgrowth in pediatric patients with intestinal failure. The focus is to address current diagnostic tools and understand their associated advantages and disadvantages based on a literature search. Culture of small intestinal aspirates, noninvasive breath tests and an emerging interest in quantitative bacterial DNA fingerprinting are discussed. Proper management is critical for preventing the recurrence of small intestinal bacterial overgrowth and its related complications. Antibiotic prophylaxis is one approach to the treatment of bacterial overgrowth in intestinal failure patients. Although treatment trials can be challenging in such a vulnerable population, more investigative clinical studies examining early diagnosis, more effective control of recurrence and the prevention of associated complications must be conducted.     

Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test,suggesting bacterial overgrowth

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case–control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 ± 0.8 in IBS subjects and 2.2 ± 1.0 in controls (P < 0.000001). The duration of phase III was 305 ± 123 sec in IBS subjects and 428 ± 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.     

Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon

AIM: Small intestinal bacterial overgrowth (SIBO) may contribute to the appearance of several gastrointestinal nonspecific symptoms. Acute diverticulitis is affected by some similar symptoms and bacterial colonic overgrowth. We assessed the prevalence of SIBO in acute uncomplicated diverticulitis and evaluated its influence on the clinical course of the disease. METHODS: We studied 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32-91 years). Sixty-one patients (67.78%) and 29 patients (32.22%) were affected by constipation-or diarrhea-prevalent diverticulitis respectively. All subjects were investigated by lactulose H_2-breath test at the entry and at the end of treatment. We also studied a control group of 20 healthy subjects (13 males, 7 females, mean age 53 years, range 22-71 years). RESULTS: Oro-cecal transit time (OCTT) was delayed in 67/90 patients (74.44%) (range 115-210 min, mean 120 min). Fifty-three of ninety patients (58.88%) showed SIBO, while OCTT was normal in 23/90 patients (25,56%). In the control group, the mean OCTT was 88.2 min (range 75-135 min). The difference between diverticulitic patients and healthy subjects was statistically significant (P＜0.01). OCTT was longer in constipation-prevalent disease than in diarrheaprevalent disease [180.7 min (range 150-210 min) vs 121 min (range 75-180 min) (P＜0.001)], but no difference in bacterial overgrowth was found between the two forms of diverticulitis.After treatment with rifaximin plus mesalazine for 10d, followed by mesalazine alone for 8 wk, 70 patients (81.49%) were completely asymptomatic, while 16 patients (18.60%) showed only slight symptoms. Two patients (2.22%) had recurrence of diverticulitis, and two other patients (2.22%) were withdrawn from the study due to side-effects. Seventy-nine of eighty-six patients (91.86%) showed normal OCTT (range 75-105 min, mean 83 min), while OCTT was longer, but it was shorter in the remaining seven (8.14%) patients (range 105-115 min, mean of 110 min). SIBO was eradicated in all patients, while it persisted in one patient with recurrence of diverticulitis. CONCLUSION: SIBO affects most of the patients with acute diverticulitis. SIBO may worsen the symptoms of patients and prolong the clinical course of the disease, as confirmed in the case of persistence of SIBO and diverticulitis recurrence. In this case, we can hypothesize that bacteria from small bowel may re-colonize in the colon and provoke recurrence of symptoms.     

肝硬化患者小肠细菌过度生长在肠道气体产生中的作用

肝硬化是我国常见疾病和主要死亡原因之一,肝硬化患者由于门静脉高压致胃肠道瘀血、胆汁酸和胃酸的相对缺乏、肠道运动障碍等因素,可导致肠腔需氧菌增多,结肠的细菌移行至空肠和十二指肠,引起小肠细菌过度生长(small intestinal bacterial overgrowth,SIBO),继而增加内源性感染的机会[1].在临床中发现,肝硬化患者常伴有肠道气体增多,并导致肠胀气、腹胀、腹痛等症状,影响患者生活质量及增加临床治疗难度,目前肝硬化小肠细菌过度生长与肝性脑病、内毒素血症的关系研究较多[2-3],但有关肝硬化小肠细菌过度生长与肠道气体形成的研究较少.本研究通过观察肝硬化伴小肠细菌过度生长患者经过微生态制剂治疗后肠道气体的变化,旨在探讨小肠细菌过度生长在肝硬化患者肠道气体产生中的作用,希望为肝硬化患者肠道气体的治疗提供新的方向.     

肝硬化患者小肠细菌过度生长与轻微肝性脑病的相关性研究

目的探讨肝硬化患者小肠细菌过度生长与轻微肝性脑病(MHE)的相关性。方法60例肝硬化患者(肝硬化组)及20名健康志愿者(对照组)全部接受葡萄糖氢呼气试验检测小肠细菌过度生长情况,进行数字连接试验(NCT-A及NCT-BC)和数字符号试验诊断MHE。抗生素抑制小肠细菌过度生长后再进行以上试验,对比治疗前后观察指标的变化。结果对照组检出1例患者(5%)伴小肠细菌过度生长,未检出MHE。肝硬化组共检出20例(33.3%)患者伴小肠细菌过度生长,MHE 26例(43.3%),其中伴小肠细菌过度生长肝硬化患者MHE检出17例,不伴小肠细菌过度生长患者MHE检出9例。应用抗生素抑制小肠细菌过度生长1周后20例小肠细菌过度生长患者有18例葡萄糖氢呼气试验阴性,17例伴小肠细菌过度生长的MHE患者13例数字连接试验和数字符号试验正常。肝硬化患者小肠细菌过度生长与MHE存在相关性,相关系数为0.511(P<0.005)。结论部分肝硬化患者存在小肠细菌过度生长,伴小肠细菌过度生长肝硬化患者的MHE检出率高于不伴小肠细菌过度生长肝硬化患者,应用抗生素抑制小肠细菌过度生长后MHE检出率明显下降,肝硬化患者小肠细菌过度生长与MHE有相关性。     

Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms： Experience with Rifaximin

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.
METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.
RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS.
CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.     

硫化氢呼气试验在小肠细菌过度生长诊断中的应用价值初探

目的:探究硫化氢呼气试验（hydrogen sulfide breath test,SBT）在小肠细菌过度生长（small intestinal bacterial overgrowth, SIBO）诊断中的应用价值。方法:纳入2019年4—12月某高校学生,进行消化道症状和1周膳食问卷调查,以及乳果糖氢-甲烷呼气试验...     

质子泵抑制剂与小肠细菌过度增长关系的 Meta 分析

目的评价质子泵抑制剂（PPI）与小肠细菌过度增长之间的关系。方法检索MEDLINE ／PubMed、Cochrane Central Register of Controlled Trials、中国生物医学文献数据库等,按标准纳入 PPI 导致细菌过度增长的所有观察性研究。采用 Cochrane 协作网提供的 RevMan 5．1软件进行荟萃分析。结果8项观察性研究共576例患者纳入分析。结果显示,PPI 显著增加发生胃肠道细菌过度增长的风险（阳性率为46．61％）,与对照组比较差异有统计学意义[风险比（OR）＝13．46,95％可信区间（CI）：7．00～25．88,P ＜0．01];不同剂量 PPI 比较,20 mg／d 和40 mg／d 组细菌过度增长的阳性率分别为47．62％和39．62％;不同疗程 PPI 比较,疗程＞1个月组与对照组差异有统计学意义（OR ＝16．47％,95％CI：7．82～34．71,P ＜0．01）,而疗程＜1个月组与对照组差异无统计学意义（P ＞0．05）;细菌培养组和葡萄糖氢呼气试验组,细菌过度增长的阳性率分别为48．03％和45．87％,与对照组比较差异均有统计学意义（P ＜0．01）。结论PPI 可增加胃肠道发生细菌过度增长的风险,但短期治疗可能不影响胃酸阻止细菌定殖胃肠道的功能。     

慢性肝病小肠细菌过度生长与内毒素血症

目的观察慢性肝病患者小肠细菌过度生长(SIBO)的情况与内毒素、血小板源生长因子PDGF)水平及血清肝纤维化指标的关系。方法采用乳果糖氢呼气试验(LHBT)检测64例慢性肝病患者SIBO情况,鲎试验检测血浆内毒素,双抗体夹心ELISA检测PDGF,放免法检测透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽氨基末端肽(PⅢNP)、Ⅳ型胶原(Ⅳ.C)水平。分析SIBO与内毒素、血清肝纤维化指标之间的关系。结果64例慢性肝病患者中,LHBT阳性22例(34.4%),慢性肝病伴与不伴SIBO的血浆内毒素为(62±19)和(31±13)pg/ml;PDGF为(211±77)和(136±57)pg/ml;HA为649±189)和(394±210)ng/ml;LN为(139±24)和(110±35)μg/L;Ⅳ.C为(156±41)和(112±51)μg/L;PⅢNP为(32±10)和(21±12)μg/L(P值均<0.01)。慢性肝病患者血浆内毒素水平与PDGF水平呈直线正相关(r=0.803,P<0.01);血浆内毒素、PDGF水平与血清肝纤维化指标呈正相关。结论SIBO是慢性肝病患者出现高内毒素血症的原因之一,其引起的肠源性内毒素血症可能参与促进肝纤维化发生、发展的过程。     

Macronutrient intakes in obese subjects with or without small intestinal bacterial overgrowth: an alimentary survey

Objective: Obesity is a multifactorial disorder with a possible microbiota derangement in its pathogenesis. Moreover, in obese patients the likelihood of small intestinal bacterial overgrowth (SIBO) is greater than in controls, although few studies are currently available. This study investigates the prevalence of SIBO and the possible role of dietary macronutrients in obesity. Materials and methods: Sixty obese patients and normal lean controls were enrolled for SIBO detection. Diagnosis of SIBO was performed by a glucose breath test. A 24-hour recall questionnaire was administered to investigate macronutrient daily intake between the two obese patient subgroups (with/without SIBO). Results: The presence of SIBO in obese and controls was respectively 23.3% and 6.6% (p?=?0.02, OR?=?4.26, 95% Confidence interval?=?1.31–13.84). Obese patients with SIBO ingested more carbohydrates (252.75?±?30.53 vs 201?±?70.76 g/day, p?=?0.01), more refined sugars (104.15?±?28.69 vs 73.32?±?44.93 g/day, p?=?0.02) and less total and insoluble fibers (9.6?±?1.97 vs 14.65?±?8.80 g/day, p?=?0.04 and 4.7?±?1.11 vs 8.82?±?5.80 g/day, p?=?0.01, respectively). There were no significant differences in lipid and protein intake between the two groups. Conclusions: SIBO is widespread in obese subjects. Carbohydrates might promote the development of SIBO in obesity and fibers provide a protective function. Our results suggest a close relationship between diet and SIBO in obesity, thus supporting a possible role for intestinal microbiota.     

Differential changes in intrinsic innervation and interstitial cells of Cajal in small bowel atresia in newborns

AIM: To investigate morphological changes of the enteric nervous system (ENS) and the interstitial cells of Cajal (ICCs) in small bowel atresia.METHODS: Resected small bowel specimens from affected patients (n = 7) were divided into three parts (proximal, atretic, distal). Standard histology and enzyme immunohistochemistry anti-S100, anti-protein gene product (PGP) 9.5, anti-neurofilament (NF), antic-kit-receptor (CD117) was carried out on conventional paraffin sections of the proximal and distal part. RESULTS: The neuronal and glial markers (PGP 9.5, NF, S-100) were expressed in hypertrophied ganglia and nerve fibres within the myenteric and submucosal plexuses. Furthermore, the submucous plexus contained typical giant ganglia. The innervation pattern of the proximal bowel resembled intestinal neuronal dysplasia. The density of myenteric ICCs was clearly reduced in the proximal bowel, whereas a moderate number of muscular ICCs were found. The anti-CD117 immunore- action revealed additional numerous mast cells. The distal bowel demonstrated normal morphology and density of the ENS, the ICCs and the mast cells.CONCLUSION: The proximal and distal bowel in small bowel atresia revealed clear changes in morphology and density of the ENS and ICCs.     

Ileocecal valve dysfunction in small intestinal bacterial overgrowth: A pilot study

AIM: To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.METHODS: Using a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI. The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced. The catheter was placed across the ICV so that at least one pressure port was within the TI, ICV and the cecum respectively. Pressures were continuously measured during air insufflation into the cecum, under direct endoscopic visualization, in 19 volunteers. Air was insufflated to a maximum of 40 mmHg to prevent barotrauma. All subjects underwent lactulose breath testing one month after the colonoscopy. The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation.RESULTS: Nineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope. Initial baseline readings showed no statistical difference in the pressures of the TI and ICV, between subjects with positive lactulose breath tests and normal lactulose breath tests. The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactulose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg, P = 0.0011). The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%, P = 0.0006). The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal pressures during air insufflation 21.23 ± 3.52 mmHg vs 16.10 ± 3.39 mmHg. The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflation was not significantly different 101.08% ± 7.96% vs 100% ± 0%. The total symptom score for subjects with normal lactulose breath tests and subjects with positive lactulose breath tests was not statistically different (13.30 ± 4.09 vs 24.14 ± 6.58). The ICV peak pressures during air insufflations were significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.005). The average percent difference of the area under the pressure curve in the ICV from cecum was significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.0012). Individuals with positive lactulose breath tests demonstrated symptom scores which were significantly higher for the following symptoms: not able to finish normal sized meal, feeling excessively full after meals, loss of appetite and bloating.CONCLUSION: Compared to normal, subjects with a positive lactulose breath test have a defective ICV cecal distension reflex. These subjects also more commonly have higher symptom scores.     

Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis

BACKGROUNDGut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately.AIMTo study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODSThis observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test.RESULTSSIBO was found in 24/47 (51.1%) patients. Patients with SIBO had a higher abundance of Firmicutes (P = 0.017) and Fusobacteria (P = 0.011), and a lower abundance of Bacteroidetes (P = 0.013) than patients without SIBO. This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia (P = 0.020) of the Lachnospiraceae family (P = 0.047), while the abundance of other major families of this phylum [Ruminococcaceae (P = 0.856), Peptostreptococcaceae (P = 0.066), Clostridiaceae (P = 0.463), Eubacteriaceae (P = 0.463), Lactobacillaceae (P = 0.413), and Veillonellaceae (P = 0.632)] did not differ significantly between the patients with and without SIBO. Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum [Bacteroidaceae (P = 0.014), Porphyromonadaceae (P = 0.002), and Rikenellaceae (P = 0.047)], with the exception of Prevotellaceae (P = 0.941). There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis [Proteobacteria (P = 0.790), Bacilli (P = 0.573), Enterobacteriaceae (P = 0.632), Streptococcaceae (P = 0.170), Staphylococcaceae (P = 0.450), and Enterococcaceae (P = 0.873)] between patients with and without SIBO.CONCLUSIONDespite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.     

糖尿病大鼠小肠Cajal间质细胞及干细胞因子的变化及半夏泻心汤的干预作用

[目的]观察糖尿病（diabetes mellitus,DM）大鼠小肠Cajal间质细胞（ICC）及干细胞因子（stem cell faetor,SCF）表达的变化及半夏泻心汤的干预作用。[方法]除10只大鼠作为正常组外,其他大鼠采用腹腔注射STZ复制DM模型后随机分为DM组、半夏泻心汤组及西药组。半固体营养糊灌胃测定各组大鼠小肠推进率,免疫组化检测c-Kit及SCF在小肠组织中的表达;Western blot检测小肠组织c-Kit蛋白、SCF蛋白表达。[结果]半夏泻心汤组与西药组大鼠的体质量、小肠推进率、c-Kit及SCF阳性细胞数、c-Kit蛋白及SCF蛋白的表达均较DM组明显增加（均P〈o．05）;半夏泻心汤组与西药组大鼠的血糖值较DM组明显降低（P〈0．05）。半夏泻心汤组与西药组之间差异无统计学意义（均P〉0．05）。[结论]半夏泻心汤可以促进DM大鼠小肠肌间神经丛c-Kit、SCF的表达,提示对受损的DM大鼠小肠ICC、SCF有部分恢复作用,从而对DM大鼠的小肠动力障碍有一定的改善作用。     

小鼠不全性肠梗阻对Cajal间质细胞表型的影响

目的:探讨小鼠小肠慢性不全性肠梗阻导致自发性节律性收缩运动、电活动变化与Cajal间质细胞(ICC)表型转化的关系.方法:通过外科手术方法在小鼠回肠套入硅胶管,建立小鼠不全性肠梗阻模型.利用苏木精-伊红(H&E)染色,研究小肠平滑肌层形态学改变;利用常规生理和电生理技术观察环行平滑肌肌条自发性节律性收缩和慢波变化规律;利用全层平滑肌免疫组织化学方法,观察ICC表型标志酪氨酸激酶受体(c-kit)表达的变化.结果:小鼠不全性肠梗阻模型形成后14d,梗阻近端肠管显著扩张、小肠平滑肌层明显增生肥厚;小肠平滑肌自发性节律性收缩节律紊乱、幅度不规则、频率变慢;平滑肌静息膜电位去极化、慢波幅度变小、频率变慢;ICC表型标志c-kit表达显著减弱、甚至消失.结论:小鼠不全性肠梗阻导致机械和电活动紊乱与ICC表型转化导致的ICC数量减少和网络破坏有关.该模型为进一步研究ICC表型改变的细胞/分子机理提供了一个良好的实验模型.     

Diagnosis and treatment of small intestinal bacterial overgrowth

A huge number of bacteria are hosted in the gastrointestinal tract, following a gradient increasing towards the colon. Gastric acid secretion and intestinal clearance provide the qualitative and quantitative partitioning of intestinal bacteria; small intestinal bacteria overgrowth (SIBO) occurs when these barrier mechanisms fail. Diagnosis of SIBO is challenging due to the low specificity of symptoms, the frequent association with other diseases of the gastrointestinal tract and the absence of optimal objective diagnostic tests. The therapeutic approach to SIBO is oriented towards resolving predisposing conditions, and is supported by antibiotic treatment to restore the normal small intestinal microflora and by modifications of dietary habits for symptomatic relief. In the near future, metagenomics and metabolomics will help to overcome the uncertainties of SIBO diagnosis and the pitfalls of therapeutic management, allowing the design of a personalized strategy based on the direct insight into the small intestinal microbial community.