Mechanism Research On The Symptoms Occurrence Of Lactose Intolerance

Lactase deficiency happens all over the world. And Lactase malabsorption (LM) in gastrointestinal tract resulting from Lactase deficiency will produce gas and short chain fatty acids (SCFAs) which will stimulate abdominal discomfort (i.e. Lactose intolerance, LI). But Lactase malabsorption does not necessarily results in Lactose intolerance, which will be especially confusing in diseases without apparently organic disease like Irritable bowel syndrome (IBS). Several studies found similar prevalence of Lactase malabsorption between IBS patients and healthy people, but more Lactose intolerance in IBS patients. The underlying reasons are still not clear, but the psychological factors and visceral sensitivity that are closely related IBS deserve investigation.The effects of Small intestinal bacterial overgrowth (SIBO) on non-organic disease have been provoked by many authors. Some of them proved that IBS patients have more SIBO than normal people. SIBO and Lactose intolerance share similar mechanism on the symptoms occurrence. Previous studys have demonstrated that SIBO can increase the prevalence of Lactase malabsorption, but few reports focus on the influence to Lactose intolerance.There is no'gold standard' on SIBO diagnosis test and those currently used are also need to be improved and validated. PART ONE The effects of gas excretion, visceral sensitivity and psychological stress on lactose intoleranceAIMS:to detect the difference of LI occurrence between IBS-D patients and normal individual by lactose HBT. To study the role of gas excretion, visceral sensitivity and psychological stress on mechanism of LI symptoms occurrence. SUBJECTS:Forty-one consecutive out-patients with the diagnosis of IBS-D and thirty-seven healthy controls were involved in this study.METHODS:All subjects completed standard questionnaires and a simple, short-protocol barostat study to evaluate their psychological states and visceral hypersensitivity. Lactose HBT were performed in a double-blind way.RESULTS:The patients of IBS-D group are much more sensitive to all these three doses of lactose (p20g=0.007), however, the prevalence of lactose maldigestion is similar among these groups. The scores of anxiety and life events were higher in IBS-D group than control group (p=0.028; p=0.001). There were no difference of psychological states in IBS-D pts between intolerance and tolerance group classified by HBT. But in healthy, the intolerance group got higher scores of anxiety than tolerance group (p20g=0.003). In pts group, the time of H2 initial rising was earlier in symptomatic group than non-symptomatic (p20g=0.041). The sensory, urgent and discomfort/pain threshold were lower in IBS-D pts than in controls (p=0.009; p=0.007; p=0.003;p<0.001).CONCLUSIONS:Visceral sensitivity and psychological stress are correlated well with IBS-D, but don't influence the onset of lactose intolerance symptoms. In healthy individual, psychological state is associated with LI when lactose HBT.PART TWO Study on the diagnosis test of SIBOAIMS:to compare three different tracer's effect (barium sulfate/Cardiografin/ 99mTc-DTPA) on lactulose hydrogen breath test (LHBT).SUBJECTS:13 healthy subjects without abdominal complaints were recruited, all of them were H2 producer by previous HBT.METHODS:All subjects completed lactulose HBT/scintigraphy. The oro-caecal transit time (OCTT) was defined objectively as the time at which at least 10% of administered dose of isotopes had accumulated in the caecal region.4 subjects also completed LHBT/barium sulfate and LHBT/Cardiografin. Test interval was more than one week.RESULTS:In LHBT/barium sulfate test, barium sulfate were found still stagnating in small intestine by abdominal X-ray when H2 value were> 20ppm above basal in all 4 subjects. In LHBT/Cardiografin test, we did not clearly identity the forehead of Cardiografin through X-ray when H2 value were> 20ppm above basal in all 4 subjects. In LHBT/scintigraphy, the time of 5ppm rising in H2 correlated well with OCTT (p＜0.001).CONCLUSIONS:Compared with barium sulfate and Cardiografin,99mTc-DTPA shows better correlation with H2 rising. So LHBT combined with 99mTc-DTPA is good candidate for SIBO diagnosis.PART THREE The effects of small intestinal bacterial overgrowth on lactose intoleranceAIMS:to evaluate whether there is different prevalence of SIBO between non-organic chronic diarrhea and normal people. And the underlying mechanism of disease and cause of symptoms was assessed.SUBJECTS:Consecutive out-patients referred for chronic diarrhoea and no alarm symptoms or other evidence of relevant organic diseases were investigated prospectively. Lactose hydrogen breath test (HBT) findings from healthy individuals with no history of gastrointestinal symptoms are provided as healthy control data.METHODS:All participants completed standard questionnaires to assess symptoms (Rome III questionnaire), and the presence of psychological disease (HAD/ RLCQ), then underwent a validated 20 g lactose HBT. Patients completed also a 10 g LHBT with concurrent assessment of small bowel transit by scintigraphy. Patients diagnosed with SIBO were required to take antibiotics treatment (rifaximin,1200mg/d 7days). Therapeutic effect were followed up a month later.RESULTS:A total of 31 subjects with chronic diarrhoea and 32 controls were enrolled. Patients and controls were well matched for age and gender (p>0.05). The two group had similar LM (27/31 vs.29/32 p=0.708), but LI happened more frequently in patients than controls(14/27 vs.5/29 p<0.01). SIBO was present in 11/27 subjects with LM (41%). the prevalence of SIBO was significantly higher in LI patients than in the LM control group [9/14(64.3%) vs.2/13(15.4%), P= 0.018]. The early appearance of symptoms during the lactose HBT was strongly associated with the severity of symptoms (TSS) in LI patients (r=0.730, P=0.003) and subgroup analysis revealed that this association was present in SIBO patients (r=0.781, P= 0.013), but not in those without SIBO. There was a significant association between the time at which H2 excretion peaked (r=0.412; P=0.033), maximum H2 concentration measured (r= 0.534; P=0.004) and H2 excretion AUC (r= 0.568, P= 0.002) during the lactose and lactulose HBTs.7 of 9 subjects successfully followed up reported obvious improvement after SIBO eradication,3 of them completely symptoms free. There was no significant difference on the HAD scale in SIBO positive and negative pts. The OCTT was similar between the LI and LM groups (P= 0.253) and there was no important difference of OCTT between patients with and without SIBO (P= 0.704).CONCLUSIONS:this study shows that SIBO greatly increases the likelihood of symptoms occurring after lactose ingestion in patients with chronic diarrhoea because fermentation and gas production in the small bowel are more likely to cause symptoms than the same process in the colon. There are no correlation between SIBO with psychological stress and GI motility.