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1.
Lactose digestion in humans: intestinal lactase appears to be constitutive whereas the colonic microbiome is adaptable.
Forsgård, RA
The American journal of clinical nutrition. 2019;(2):273-279
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Abstract
Globally, ∼70% of adults are deficient in intestinal lactase, the enzyme required for the digestion of lactose. In these individuals, the consumption of lactose-containing milk and dairy products can lead to the development of various gastrointestinal (GI) symptoms. The primary solution to lactose intolerance is withdrawing lactose from the diet either by eliminating dairy products altogether or substituting lactose-free alternatives. However, studies have shown that certain individuals erroneously attribute their GI symptoms to lactose and thus prefer to consume lactose-free products. This has raised the question whether consuming lactose-free products reduces an individual's ability to absorb dietary lactose and if lactose-absorbers should thus avoid these products. This review summarizes the current knowledge regarding the acclimatization of lactose processing in humans. Human studies that have attempted to induce intestinal lactase expression with different lactose feeding protocols have consistently shown lack of enzyme induction. Similarly, withdrawing lactose from the diet does not reduce intestinal lactase expression. Evidence from cross-sectional studies shows that milk or dairy consumption is a poor indicator of lactase status, corroborating the results of intervention studies. However, in lactase-deficient individuals, lactose feeding supports the growth of lactose-digesting bacteria in the colon, which enhances colonic lactose processing and possibly results in the reduction of intolerance symptoms. This process is referred to as colonic adaptation. In conclusion, endogenous lactase expression does not depend on the presence of dietary lactose, but in susceptible individuals, dietary lactose might improve intolerance symptoms via colonic adaptation. For these individuals, lactose withdrawal results in the loss of colonic adaptation, which might lower the threshold for intolerance symptoms if lactose is reintroduced into the diet.
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Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.
Bashashati, M, Moossavi, S, Cremon, C, Barbaro, MR, Moraveji, S, Talmon, G, Rezaei, N, Hughes, PA, Bian, ZX, Choi, CH, et al
Neurogastroenterology and motility. 2018;(1)
Abstract
BACKGROUND & AIMS Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2 ≤ 50% and I2 > 50% indicated fixed and random effect models, respectively. KEY RESULTS Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8+ T cells. CONCLUSIONS & INFERENCES Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.
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Low colonic absorption drugs: risks and opportunities in the development of oral extended release products.
Xu, J, Lin, Y, Boulas, P, Peterson, ML
Expert opinion on drug delivery. 2018;(2):197-211
Abstract
INTRODUCTION Currently numerous drugs have been observed with lower colonic absorption than small intestine absorption, which can significantly impact in vivo performance of their oral extended release (ER) products. AREAS COVERED We reviewed over 300 publications, patents, book chapters, and commercial reports of drug products from regulatory agencies for low colonic absorption (LCA) drugs and critical findings are discussed. The focuses of this article are (1) current findings on the causes of low colonic absorption to support early assessment of LCA candidates, and (2) current knowledge on successful ER strategies and technical platforms used for LCA drugs in commercial drug products to facilitate oral ER product development. EXPERT OPINION Colonic drug absorption is one of the critical considerations in successful development of oral ER products. The root causes of low colonic absorption in many LCA drugs are still unclear. It is recommended to evaluate colonic drug absorption of drug candidate at early stage of oral ER product development. After evaluation, the selection of a formulation platform to develop an oral ER product needs to be carefully considered for LCA drugs. Based on the current commercial oral ER formulation platforms for LCA drugs, compounds are first divided into five types (I-V) and different ER formulation approaches with higher success rate are recommended for each type.
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Eosinophilic colitis: Case series and literature review.
Díaz Del Arco, C, Taxonera, C, Olivares, D, Fernández Aceñero, MJ
Pathology, research and practice. 2018;(1):100-104
Abstract
INTRODUCTION Primary eosinophilic colitis (EC) in adults is a rare and poorly studied disease, with 3 case series, 2 database-based studies and 52 case reports published to date. METHODS Retrospective study of all adult EC cases diagnosed in a large tertiary hospital (Hospital Clínico San Carlos, Madrid) between 2006 and 2016. We included all cases with a histopathological diagnosis of EC and we selected only those cases that were clinically recognized primary EC. We report their clinical, endoscopic and histopathological features and review the literature on this topic. RESULTS We identified 22 primary EC cases. Patients were mostly women (77%) with a mean age of 41 years. 4 patients (18%) had coexistent allergic diseases. Most patients consulted with diarrhea (86%) and 3 patients also suffered from rectal bleeding. Blood tests showed peripheral eosinophilia in 4 cases (18%). 19 patients had no endoscopic lesions, 2 had features of unspecific colitis and one showed features suggestive of IBD. Mean and maximum number of eosinophils per high power field ranged from 16 to 199 and 20 to 253 (mean: 48 and 70). They were mainly located in the lamina propria and most cases were associated with signs of eosinophil activation. Most patients were treated by corticosteroids, diet or budesonide and the result of treatment was generally good. No complications or recurrences were reported. CONCLUSIONS EC etiology and pathogenesis is unknown. Its clinical, endoscopical and imaging features are not specific, and clear histopathological criteria are lacking. Identification of signs of eosinophilic activation could be helpful.
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Goal-directed fluid therapy versus conventional fluid therapy in colorectal surgery: A meta analysis of randomized controlled trials.
Xu, C, Peng, J, Liu, S, Huang, Y, Guo, X, Xiao, H, Qi, D
International journal of surgery (London, England). 2018;:264-273
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Abstract
OBJECTIVES This meta-analysis was conducted to compare the effects of goal-directed fluid therapy (GDFT) versus conventional fluid therapy (CFT) in colorectal surgery on patients' postoperative outcome and to detect whether the results differ between studies with the Enhanced Recovery After Surgery (ERAS) protocol and those without, between studies using different devices for GDFT, or between different surgical approaches (laparoscopy or laparotomy). METHODS The Cochrane Library, PubMed, Embase, Wanfang Data and ClinicalTrials.com were searched for studies from January,1990 to February, 2018. Randomized controlled trials (RCTs) comparing both two abovementioned fluid therapy protocols in colorectal surgery were included. The primary outcome was 30-day mortality after surgery. Secondary outcomes were length of hospital stay (LOS), complication rate, ICU admission and gastrointestinal indicators. RESULTS Eleven studies were included, including a total of 1281 patients: the GDFT group included 624 patients and the control group included 657 patients. No significant differences were found between groups in 30-day mortality (relative risk, RR 0.86,0.28 to 2.63, P = 0.79), LOS (weighted mean difference, WMD 0.22,-0.1 to 0.55, P = 0.18), and ICU admission (RR 0.42, 0.17 to 1.04, P = 0.06). However, the GDFT group had a lower complication rate (RR 0.84,0.71 to 0.99, P = 0.04). In subgroup analyses, time to first flatus and time to tolerate an oral diet were shorter in GDFT group than the control group in studies who did not use the ERAS protocol. No publication bias was identified according to Begg's test. CONCLUSION Compared with conventional fluid therapy, GDFT may not improve patients' postoperative outcome in colorectal surgery. However, the improvement of gastrointestinal function associated with GDFT over conventional fluid therapy was significant in the surgeries that did not use the ERAS protocol.
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Diet, Microbiota, and Metabolic Health: Trade-Off Between Saccharolytic and Proteolytic Fermentation.
Korpela, K
Annual review of food science and technology. 2018;:65-84
Abstract
The intestinal microbiota have emerged as a central regulator of host metabolism and immune function, mediating the effects of diet on host health. However, the large diversity and individuality of the gut microbiota have made it difficult to draw conclusions about microbiota responses to dietary interventions. In the light of recent research, certain general patterns are emerging, revealing how the ecology of the gut microbiota profoundly depends on the quality and quantity of dietary carbohydrates and proteins. In this review, I provide an overview of the dependence of microbial ecology in the human colon on diet and how the effects of diet on host health depend partially on the microbiota. Understanding how the individual-specific microbiota respond to short- and long-term dietary changes and how they influence host energy homeostasis will enable targeted interventions to achieve specific outcomes, such as weight loss in obesity or weight gain in malnutrition.
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Effect of gum chewing on ameliorating ileus following colorectal surgery: A meta-analysis of 18 randomized controlled trials.
Liu, Q, Jiang, H, Xu, D, Jin, J
International journal of surgery (London, England). 2017;:107-115
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Abstract
BACKGROUND AND OBJECTIVE Chewing gum, as an alternative to sham feeding, had been shown to hasten the recovery of gut function following abdominal surgery. However, conclusions remained contradictory. We sought to conduct an updated meta-analysis to evaluate the efficacy of gum chewing in alleviating ileus following colorectal surgery. METHODS We searched PubMed, EMBASE, and Cochrane Library Databases through February 2017 to identify randomized controlled trials (RCTs) evaluating the efficacy of the additional use of chewing gum following colorectal surgery. After screening for inclusion, data extraction, and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. The outcomes of interest were the time to first flatus, time to first bowel movement, length of hospital stay, and some clinically relevant parameters. We also performed subgroup analyses according to the type of surgical approaches or on trials that adopted enhanced recovery after surgery (ERAS) protocol or sugared gum. RESULTS A total of 18 RCTs, involving 1736 patients, were included. Compared with standardized postoperative care, Chewing gum resulted in a shorter passage to first flatus [WMD = -8.81, 95%CI: (-13.45, -4.17), P = 0.0002], earlier recovery of bowel movement [WMD = -16.43, 95%CI: (-22.68, -10.19), P < 0.00001], and a reduction in length of hospital stay [WMD = -0.89, 95%CI: (-1.72, -0.07), P = 0.03]. Chewing gum was also associated with a lower risk of postoperative ileus [OR = 0.41, 95%CI: (0.23, 0.73), P = 0.003]. No evidence of significant advantages in overall postoperative complication, nausea, vomiting, bloating, readmission and reoperation towards the addition of chewing gum was observed. Subgroup analyses all favored gum chewing. However, the findings are hampered by the significant heterogeneity between trials. CONCLUSIONS Based on current evidence, chewing gum offers an inexpensive, well-tolerated, safe and effective method to ameliorate ileus following colorectal surgery. However, tightly controlled, randomized and considerably larger multicenter trials are warranted to further validate our findings.
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Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis.
Sivaprakasam, S, Bhutia, YD, Yang, S, Ganapathy, V
Comprehensive Physiology. 2017;(1):299-314
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Abstract
Short-chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated in colon by bacterial fermentation of dietary fiber. Though diffusion in protonated form is a significant route, carrier-mediated mechanisms constitute the major route for the entry of SCFA in their anionic form into colonic epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1 (SLC16A1) and MCT4 (SLC16A3) are H+-coupled and mediate electroneutral transport of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+-coupled; SMCT1-mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas SMCT2-mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1 and SMCT2 are expressed exclusively in the apical membrane. An anion-exchange mechanism also operates in the apical membrane in which SCFA entry in anionic form is coupled to bicarbonate efflux; the molecular identity of this exchanger however remains unknown. All these transporters are subject to regulation, notably by their substrates themselves; this process involves cell-surface receptors with SCFA as signaling molecules. There are significant alterations in the expression of these transporters in ulcerative colitis and colon cancer. The tumor-associated changes occur via transcriptional regulation by p53 and HIF1α and by promoter methylation. As SCFA are obligatory for optimal colonic health, the transporters responsible for the entry and transcellular transfer of these bacterial products in colonic epithelium are critical determinants of colonic function under physiological conditions and in disease states. © 2018 American Physiological Society. Compr Physiol 8:299-314, 2018.
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Formation of propionate and butyrate by the human colonic microbiota.
Louis, P, Flint, HJ
Environmental microbiology. 2017;(1):29-41
Abstract
The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.
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Megacystis microcolon intestinal hypoperistalsis syndrome: Case series and updated review of the literature with an emphasis on urologic management.
Wymer, KM, Anderson, BB, Wilkens, AA, Gundeti, MS
Journal of pediatric surgery. 2016;(9):1565-73
Abstract
INTRODUCTION Megacystis microcolon intestinal hypoperistalsis (MMIHS) is a rare disorder characterized by distended nonobstructed bladder, microcolon, and decreased intestinal peristalsis. MMIHS has a particularly poor prognosis; however, when appropriately managed, survival can be prolonged. STUDY DESIGN A systematic review (1996-2016) was performed with the key words "megacystis microcolon intestinal hypoperistalsis syndrome." In addition, a case series of four patients is presented as well as algorithms for the diagnosis and treatment of MMIHS. RESULTS 135 patients with MMIHS were identified in the literature. 73% (88/121) of the patients were female, 65% underwent diagnostic biopsy (64/99), and 63% (66/106) were identified with prenatal imaging. The majority of patients were treated with TPN as well as gastrostomy or ileostomy and CIC, however 15% (18/116) received multivisceral or intestinal transplant, and 30% (22/73) had a vesicostomy. The survival rate was 57% (68/121). CONCLUSION Appropriate management of MMIHS patients is crucial. An enlarged, acontractile bladder in a child with bowel motility problems should be considered diagnostic. Bladder distension can be managed with CIC or vesicostomy in addition to prophylactic antibiotics if frequent urinary tract infections are present. These patients often require gastrostomy or ileostomy as well as total parenteral nutrition. This management has led to significant improvement in survival rates.