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Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.
Cartee, AK, Choung, RS, King, KS, Wang, S, Dzuris, JL, Anderson, RP, Van Dyke, CT, Hinson, CA, Marietta, E, Katzka, DA, et al
The American journal of gastroenterology. 2022;(2):319-326
Abstract
INTRODUCTION Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.
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Gut Microbial Carbohydrate Metabolism Hinders Weight Loss in Overweight Adults Undergoing Lifestyle Intervention With a Volumetric Diet.
Muñiz Pedrogo, DA, Jensen, MD, Van Dyke, CT, Murray, JA, Woods, JA, Chen, J, Kashyap, PC, Nehra, V
Mayo Clinic proceedings. 2018;93(8):1104-1110
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Recent research suggests that the human gut microbiome has a role to play in the development and maintenance of obesity, by influencing metabolism, fat deposition, brain-hormone signalling and insulin sensitivity. This pilot study of 26 participants, aimed to assess whether the composition and functional aspects of the gut microbiome influence outcomes of a comprehensive weight loss programme in overweight and obese individuals in America. A success criteria of 5% weight loss over a 3 month period was established. Comparisons in the gut microbiome using fecal samples at baseline and at 3 months were made between those successfully achieving the weight loss with those that did not. Achieving the weight loss success criteria was positively associated with the presence of Phascolarctobacterium. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was positively associated with a failure to lose 5% of baseline body weight after 3 months. Interestingly, Phascolarctobacterium and Dialister both belong to the same bacterial family, which suggests that a compositional shift in this family may be responsible for host carbohydrate metabolism and obesity outcomes. This study highlights the potential of influencing the gut microbiome as part of an individualised obesity management programme. However the findings need to be confirmed in a larger, cohort study over a longer duration.
Abstract
The rising incidence of obesity requires the reevaluation of our current therapeutic strategies to optimize patient outcomes. The objective of this study was to determine whether compositional and functional characteristics of the gut microbiota in adults predict responses to a comprehensive lifestyle intervention program in overweight and obese adults. We recruited 26 participants from the Mayo Clinic Obesity Treatment Research Program between August 6, 2013, and September 12, 2013, to participate in a lifestyle intervention program for weight loss. Adults aged 18 to 65 years with a body mass index of 27 to 39.9 kg/m2 and able to provide informed consent were included in the study. Fecal stool samples were obtained at baseline and after 3 months. Loss of at least 5% of baseline weight after 3 months was defined as success. Clinical characteristics and gut microbial composition and function were compared between those who achieved at least 5% and those who achieved less than 5% weight loss. After 3 months, 9 of 26 participants lost at least 5% of their weight. The mean weight loss was 7.89 kg (95% CI, 6.46-9.32 kg) in the success group and 1.51 kg (95% CI, 0.52-2.49 kg) in the less than 5% weight loss group. An increased abundance of Phascolarctobacterium was associated with success. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to lose 5% body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.
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Proton Pump Inhibitors: Review of Emerging Concerns.
Nehra, AK, Alexander, JA, Loftus, CG, Nehra, V
Mayo Clinic proceedings. 2018;(2):240-246
Abstract
First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.
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Gastric antral injections of botulinum toxin delay gastric emptying but do not reduce body weight.
Topazian, M, Camilleri, M, Enders, FT, Clain, JE, Gleeson, FC, Levy, MJ, Rajan, E, Nehra, V, Dierkhising, RA, Collazo-Clavell, ML, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013;(2):145-50.e1
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Abstract
BACKGROUND & AIMS Gastric injections of botulinum toxin A (BTA) have been reported to delay gastric emptying, increase satiation, and reduce body weight, but there are few data from randomized, placebo-controlled studies. METHODS We enrolled 60 obese participants in a 24-week, double-blind, randomized, placebo-controlled, concealed allocation trial to compare the effects of gastric antral injections of BTA (100, 300, or 500 U) and saline placebo. The study was conducted at an outpatient clinical research unit. Participants were given one set of injections of BTA or placebo into the gastric antral muscularis propria by using endoscopic ultrasound guidance. Gastric emptying of solids was measured by scintigraphy; we also measured body weight, satiation (maximum tolerated volume in a caloric liquid drink test), calorie intake (by food frequency questionnaire), gastrointestinal symptoms, and psychological aspects of eating behavior (by rating scale). RESULTS Compared with baseline values, 2 weeks after injections, the mean half-time for gastric emptying of solids increased by 0.8, 14, 24, and 14 minutes among subjects given placebo, 100, 300, or 500 U BTA, respectively (P = .24 overall, P = .04 for the group given 300 U vs placebo); 16 weeks after the injections, mean body weights were reduced by 2.2, 0.2, 2.3, and 3.0 kg in these groups, respectively. There were no statistically significant differences in mean body weight change, satiation volume, caloric intake, gastrointestinal symptoms, or psychological aspects of eating behavior among groups. CONCLUSIONS Gastric antral injections of BTA may delay gastric emptying at a dose of 300 U but do not cause early satiety, altered eating behaviors, or loss of body weight. Clinicaltrials.gov identifier: NCT00976443.
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Coingestion of whey protein and casein in a mixed meal: demonstration of a more sustained anabolic effect of casein.
Soop, M, Nehra, V, Henderson, GC, Boirie, Y, Ford, GC, Nair, KS
American journal of physiology. Endocrinology and metabolism. 2012;(1):E152-62
Abstract
When consumed separately, whey protein (WP) is more rapidly absorbed into circulation than casein (Cas), which prompted the concept of rapid and slow dietary protein. It is unclear whether these proteins have similar metabolic fates when coingested as in milk. We determined the rate of appearance across the splanchnic bed and the rate of disappearance across the leg of phenylalanine (Phe) from coingested, intrinsically labeled WP and Cas. Either [¹⁵N]Phe or [¹³C-ring C₆]Phe was infused in lactating cows, and the labeled WP and Cas from their milk were collected. To determine the fate of Phe derived from different protein sources, 18 healthy participants were studied after ingestion of one of the following: 1) [¹⁵N]WP, [¹³C]Cas, and lactose; 2) [¹³C]WP, [¹⁵N]Cas, and lactose; 3) lactose alone. At 80-120 min, the rates of appearance (R(a)) across the splanchnic bed of Phe from WP and Cas were similar [0.068 ± 0.010 vs. 0.070 ± 0.009%/min; not significant (ns)]. At time 220-260 min, Phe appearance from WP had slowed (0.039 ± 0.008%/min, P < 0.05) whereas Phe appearance from Cas was sustained (0.068 ± 0.013%/min). Similarly, accretion rates across the leg of Phe absorbed from WP and Cas were not different at 80-120 min (0.011 ± 0.002 vs. 0.012 ± 0.003%/min; ns), but they were significantly lower for WP (0.007 ± 0.002%/min) at 220-260 min than for Cas (0.013 ± 0.002%/min) at 220-260 min. Early after meal ingestion, amino acid absorption and retention across the leg were similar for WP and Cas, but as rates for WP waned, absorption and assimilation into skeletal muscle were better retained for Cas.
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Endoscopic ultrasound-guided gastric botulinum toxin injections in obese subjects: a pilot study.
Topazian, M, Camilleri, M, De La Mora-Levy, J, Enders, FB, Foxx-Orenstein, AE, Levy, MJ, Nehra, V, Talley, NJ
Obesity surgery. 2008;(4):401-7
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Abstract
BACKGROUND Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects. METHODS Open label study of ten healthy, obese adults (age = 29-49 years, body mass index = 31-54 kg/m(2)) who received 100 U (n = 4) or 300 U (n = 6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight. RESULTS For the entire cohort, MTV decreased from 1,380 cc (range: 474-2,014) at baseline to 620 cc (range: 256-1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p = 0.03). Average body weight loss was 4.9 (+/-6.3) kg after 16 weeks. Gastric emptying T(1/2) was prolonged in the 300 U BTA group, but not significantly different from baseline (p = 0.17). BTA injections were well tolerated without significant adverse effects. CONCLUSION EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.
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An open trial of octreotide long-acting release in the management of short bowel syndrome.
Nehra, V, Camilleri, M, Burton, D, Oenning, L, Kelly, DG
The American journal of gastroenterology. 2001;(5):1494-8
Abstract
OBJECTIVES The aim of this study was to assess the effects of the long-acting release (LAR) depot octreotide preparation Sandostatin LAR Depot on stool water and electrolyte losses, fecal fat excretion, and GI transit in patients with short bowel syndrome. METHODS We performed a 15-wk, prospective, open-label study of intramuscular (i.m.) Sandostatin LAR Depot, 20 mg, at 0, 3, 7, and 11 wk. Balance studies were performed before and at the end of the 15-wk study. Baseline and posttreatment measurements of body weight, stool fat, sodium and potassium, and gastric and small bowel transit of a radiolabeled egg meal were compared by paired analysis. RESULTS We studied eight patients with short bowel syndrome (five women and three men; mean age 52 yr, range 37-72 yr) who had been TPN dependent for a mean of 11.8 yr (range 1.5-22 yr). The underlying diagnoses were Crohn's disease (n = 6), intestinal ischemia (n = 1), and resection for carcinoid tumor (n = 1). Treatment with Sandostatin LAR Depot significantly increased small bowel transit time (p = 0.03). Changes in body weight, urine volume, stool weight, fecal fat excretion, stool sodium and potassium excretion, or gastric emptying rate were highly variable, and no overall significance was observed. CONCLUSIONS Sandostatin LAR Depot for 15 wk significantly prolonged small bowel transit time. Body weight and stool parameters in response to Sandostatin LAR Depot treatment needs to be assessed further in multicenter studies assessing dose, frequency of administration, and a larger sample size.
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Metabolic and nutritional considerations in nonalcoholic fatty liver.
Fong, DG, Nehra, V, Lindor, KD, Buchman, AL
Hepatology (Baltimore, Md.). 2000;(1):3-10