Aastha Malik

Relationship of cytokines, oxidative stress and GI motility with bacterial overgrowth in ulcerative colitis patients

BACKGROUND Ulcerative colitis (UC) is idiopathic, chronic and relapsing inflammatory bowel disease. Factors which initiate and perpetuate UC are not well understood. It is still unclear if any relationship exists between cytokines, oxidative stress, gastrointestinal (GI) motility, and small intestinal bacterial overgrowth (SIBO) in UC patients. GOALS To examine the relationship between these factors among UC patients. METHODS A total of 120 UC patients and 125 age and sex matched controls with no GI symptoms were enrolled. Plasma levels of IL-6, IL-8, TNF-α and IL-10 were measured in all subjects by using ELISA. Lipid peroxidation (LPO) and reduced glutathione (GSH) were measured by standard methods. Orocecal transit time (OCTT) and SIBO were measured by lactulose and glucose hydrogen breath tests respectively. RESULTS Out of the 120 UC patients, 74 were male with mean±SD age of 45.6±17.5years. Plasma levels of IL-6, IL-8, TNF-α and IL-10 in UC patients were significantly higher (p<0.01) as compared to controls. LPO in UC patients was significantly increased (p<0.01) while GSH was significantly decreased (p<0.01) as compared to controls. OCTT and SIBO were significantly higher in UC patients as compared to controls. UC patients with elevated inflammatory cytokines showed delayed OCTT and increased SIBO. It was also observed that there was a significant correlation between SIBO with IL-6, IL-8, TNF-α, and IL-10, LPO and GSH. CONCLUSION This study indicates that increase in cytokines and decrease in anti-oxidants in UC patients would have resulted in oxidative stress causing delayed GI motility leading to SIBO.

Breath tests and irritable bowel syndrome.

Breath tests are non-invasive tests and can detect H₂ and CH₄ gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath. These tests are used in the diagnosis of carbohydrate malabsorption, small intestinal bacterial overgrowth, and for measuring the orocecal transit time. Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome (IBS)-type symptoms such as diarrhea and/or constipation, bloating, excess flatulence, headaches and lack of energy. Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life. It may reflect dietary imbalance, such as excess fiber intake, or may be a manifestation of IBS. However, bloating may also represent small intestinal bacterial overgrowth. Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H₂ breath testing to determine the presence or absence of bacterial overgrowth. If bacterial overgrowth is identified, patients are typically treated with antibiotics. Evaluation of IBS generally includes testing of other disorders that cause similar symptoms. Carbohydrate malabsorption (lactose, fructose, sorbitol) can cause abdominal fullness, bloating, nausea, abdominal pain, flatulence, and diarrhea, which are similar to the symptoms of IBS. However, it is unclear if these digestive disorders contribute to or cause the symptoms of IBS. Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS. Thus, diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients.

N‐acetyltransferase 2, cytochrome P4502E1 and glutathione S‐transferase genotypes in antitubercular treatment‐induced hepatotoxicity in North Indians

Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S‐transferase (GST) gene polymorphisms may play an important role in ATT‐induced hepatotoxicity. So, elucidating the genetics involved in anti‐TB drug‐induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT‐induced hepatotoxicity in North Indian patients.

Hydrogen Breath Tests in Gastrointestinal Diseases

Hydrogen breath tests are widely used to explore pathophysiology of functional gastrointestinal (GI) disorders. Small intestinal bacterial overgrowth (SIBO) and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms of GI diseases. Glucose hydrogen breath test is more acceptable for diagnosis of SIBO whereas lactose and fructose hydrogen breath tests are used for detection of lactose and fructose maldigestion respectively. Lactulose hydrogen breath test is also used widely to measure the orocecal transit time for GI motility. These methods are noninvasive and inexpensive. Many patients with functional gut disorders are unaware of the relationship between diet and GI symptoms they present. In particular, patients with chronic symptoms may regard their condition as normal and may not be aware that their symptoms can be effectively managed following a proper diagnosis. Patients with symptoms of abdominal pain, bloating, flatulence and altered bowel movements (diarrhea and constipation), or with a medical diagnosis of irritable bowel syndrome or celiac disease, may have undiagnosed carbohydrate malabsorption or SIBO. Hydrogen breath tests are specific and sensitive diagnostic tests that can be used to either confirm or eliminate the possibility of carbohydrate malabsorption or SIBO in such patients. Breath tests, though valuable tools, are underutilized in evaluating dyspepsia and functional bloating and diarrhea as well as suspected malabsorption. However, because of their simplicity, reproducibility and safety of procedure they are now being substituted to more uncomfortable and expensive techniques that were traditionally used in gastroenterology.

A relationship between vitamin D, parathyroid hormone, calcium levels and lactose intolerance in type 2 diabetic patients and healthy subjects

BACKGROUND Type 2 diabetes mellitus is chronic metabolic disorder. Common gastrointestinal symptoms in type 2 diabetic patients are flatulence, constipation and/or diarrhea. Reason for these may be lactose intolerance leading to change in vitamin D, Calcium and parathyroid hormone which further regulate bone mineralization. AIM To measure lactose intolerance, vitamin D, calcium and parathyroid hormone in type 2 diabetic patients. MATERIAL AND METHODS 150 type 2 diabetic patients attending Endocrinology Clinic in PGI, Chandigarh and 150 age and sex matched healthy controls were enrolled. Lactose intolerance was measured using non-invasive lactose breath test. 25-hydroxyvitamin D (total) and Parathyroid hormone were measured in plasma using immunoassay. Serum calcium was measured using auto analyzer. T score was recorded from DXA scan for bone mineral density measurement. RESULTS Lactose intolerance was observed significantly higher (p<0.001) diabetic patients (59.3%) as compared to controls (42%). Levels of plasma 25-OH vitamin D (total), parathyroid hormone and serum calcium were significantly lower in patients as compared to controls. Furthermore, levels of plasma 25-OH vitamin D (total), parathyroid hormone and serum calcium were more decreased in lactose intolerant diabetic patients than lactose tolerant patients. Sixty seven percent (67%) of diabetic patients suffered from osteoporosis and 20% of controls. Eighty percent (80%) diabetic patients and 16% controls with osteoporosis suffered from lactose intolerance. CONCLUSION From this study we can conclude that measurement of lactose intolerance using non-invasive lactose breath test is suggested for type 2 diabetic patients along with timely measurement of 25-OH vitamin D (total), calcium and parathyroid hormone levels.

Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth

Oxidative stress is risk factor in progression of diabetes. It can increase cytokine production via several different mechanisms. Inflammation can affect gut neural apparatus that may lead to dysmotility which may exaggerate occurrence of bacterial overgrowth in intestine. Thus, a study was planned to understand the complex interplay of oxidative stress, inflammatory cytokines, gut motility and small intestinal bacterial overgrowth in type 1 diabetes mellitus (T1DM) patients.

Effect of Post-Cholecystectomy on Small Intestinal Bacterial Overgrowth and Orocecal Transit Time in Gallstone Patients

Background: Effect of duration of cholecystectomy on orocecal transit time and small intestinal bacterial overgrowth in gallstone patients is poorly understood. Method: 128 gallstone patients of either sex, aged between 25-68 years were enrolled. 79/128 followed after 4-6 months of cholecystectomy. 49 patients had undergone cholecystectomy 2 - 15years before study and reported gastrointestinal symptoms, classified as late post-cholecystectomy. Orocecal transit time (OCTT) and small intestinal bacterial overgrowth (SIBO) were measured by non-invasive lactulose and glucose breath tests respectively. Results: OCTT increased significantly (p < 0.01) from 125.9 ± 28.6 to 145.8 ± 30.5 minutes after 4-6 months of cholecystectomy. Among late post-cholecystectomy patients, OCTT was observed to be 159.2 ± 37.8 minutes, which was significantly higher when compared with OCTT in pre-cholecystectomy patients. SIBO was present in 10/79 (12.7%) gallstone patients pre-cholecystectomy and 11/79 (13.9%) in gallstone patients post-cholecystectomy. Presence of SIBO after 4-6 months of cholecystectomy was not significantly different compared to pre-cholecystectomy in gallstone patients. However, SIBO was present in 13 / 49 (26.5%) late post-cholecystectomy patients with duration of 2-15years, which was significantly (p < 0.05) higher compared to pre-cholecystectomy and 4-6months post-cholecystectomy patients. Conclusion: The study signifies that longer duration of post-cholecystectomy can lead to delayed OCTT and cause SIBO in gallstone patients. This can be mitigated by giving pro-kinetics to post-cholecystectomy patients.