Publications by authors named "Stephen J D O'Keefe"

Introduction: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC).

Methods/design: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit.

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Epidemiological trends have led to a growing consensus that diet plays a central role in the etiopathogenesis of inflammatory bowel diseases (IBD). A Western diet high in ultra-processed foods has been associated with an increased prevalence of IBD worldwide. Much attention has focused on components of the Western diet, including the high fat content, lack of fiber, added sugars, and use of additives, such as carrageenan and other emulsifiers.

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Article Synopsis
  • - The symposium aimed to connect Western microbiome experts with African researchers to explore the unique differences in disease patterns seen in Africa, particularly focusing on infectious diseases versus noncommunicable diseases (NCDs) prevalent in developed countries.
  • - Recent findings suggest that traditional African diets rich in fiber may help reduce the risk of NCDs, but there is growing concern that migration and shifting diets toward Western foods are increasing the prevalence of these diseases in Africa.
  • - There is an urgent call for collaborative research between Africa and the West to understand the diet-microbiome relationship better and to prevent the rising incidence of NCDs in Africa while also addressing healthcare challenges found in developed nations.
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Introduction: Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide.

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A one-vial extraction method for the quantitation of short-chain fatty acids (SCFAs) in human stool was developed. Samples were extracted with an acidified aqueous internal standard solution, sodium sulfate, and diethyl ether, followed by analysis with GC-FID. Accuracy, in terms of relative recovery, was typically between 90 and 110% for most analytes; without internal standard, the accuracy was about 5-34%; the linear dynamic range (LDR) was 0.

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Article Synopsis
  • Colorectal cancer (CRC) risk is heavily influenced by dietary habits, particularly a high intake of dietary fat, which can lead to the development of pre-cancerous lesions and worsen colonic tumor formation.
  • High-fat diets alter gut microbiota and bile acid metabolism, resulting in increased secondary bile acids that promote tumor activity in the colon.
  • The farnesoid X receptor (FXR) plays a crucial role in regulating the effects of bile acids on intestinal tumor growth, highlighting the interaction between diet, gut bacteria, and genetic factors in influencing CRC risk.
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  • This review highlights recent studies on how dietary changes and nutritional interventions impact the human microbiome across various regions, emphasizing benefits of fiber-rich foods in preventing diseases.
  • It shows that disruptions to the microbiome in impoverished areas can lead to chronic malnutrition and underlines the critical role of breastfeeding.
  • The findings reveal significant shifts in microbial composition and metabolic products with dietary changes, but point out the need for further research to measure their health benefits more accurately.
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  • - Alaska Native (AN) people have the highest known rate of colorectal cancer (CRC) globally, while rural Africans (RA) have the lowest, suggesting that dietary differences may influence CRC risk through their effect on gut microbiota.
  • - A study compared the dietary habits and gut microbiota of healthy middle-aged volunteers from AN and RA, revealing that AN participants had higher fat and animal protein intake, lower fiber, and a distinct microbial composition linked to tumor-promoting metabolites.
  • - Results showed that AN individuals had adenomatous polyps and lower butyrate levels, a tumor-suppressive metabolite, alongside higher levels of deoxycholic acid, a tumor-promoting substance; thus, the differing metabolite profiles
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Article Synopsis
  • The review examines how fiber and fat in the diet affect the risk of colorectal cancer (CRC), highlighting a significant relationship between fiber intake and reduced CRC risk.
  • Increased dietary fiber is linked to higher butyrate production by gut bacteria, which has anti-cancer properties, while high-fat diets can elevate CRC risk by promoting the production of harmful bile acids.
  • The study suggests that managing fiber consumption and limiting fat intake could be effective strategies to lower CRC risk, although more research is needed to understand the underlying mechanisms and interactions between these dietary components.
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Background: The effect of diet on risk of acute pancreatitis (AP) has been suggested by prior studies, but the association of dietary habits with severity of AP has not been previously evaluated.

Objective: The objective of the study was to assess differences in reported dietary habits in patients with severe AP compared with those with mild or moderate AP.

Methods: A prospectively maintained cohort of patients with AP was utilized.

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This article provides evidence that current dietary fiber intake levels may be insufficient to maintain colonic mucosal health and defense, and reduce inflammation and cancer risk in otherwise healthy people. Current commercial tube feeds generally overlook the metabolic needs of the colon and may predispose patients to dysbiosis, bacterial overgrowth with pathogens such as Clostridium difficile, and acute colitis. These results raise concern about the wide-scale use of prophylactic antibiotics in the intensive care unit and the use of elemental, fiber-depleted tube feeds.

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Objectives: Despite the fact that the most effective treatment for morbid obesity today is gastric bypass surgery, some patients develop life-threatening nutritional complications associated with their weight loss.

Methods: Here we examine the influence of the altered anatomy and digestive physiology on pancreatic secretion and fat absorption. Thirteen post Roux-en-Y gastric bypass (RYGB) patients who had lost >100 lbs in the first year following surgery and who gave variable histories of gastrointestinal (GI) dysfunction, were selected for study.

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Colorectal cancer is one of the so-called westernized diseases and the second leading cause of cancer death worldwide. On the basis of global epidemiological and scientific studies, evidence suggests that the risk of colorectal cancer is increased by processed and unprocessed meat consumption but suppressed by fibre, and that food composition affects colonic health and cancer risk via its effects on colonic microbial metabolism. The gut microbiota can ferment complex dietary residues that are resistant to digestion by enteric enzymes.

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Objectives: In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide.

Methods: Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment.

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In this review, I focus on the extreme of the short bowel syndrome where the loss of intestine is so great that patients cannot survive without intravenous feeding. This condition is termed short bowel intestinal failure. The review outlines the principles behind diagnosis, assessing prognosis and management.

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Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association.

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Short bowel syndrome (SBS) is a heterogeneous disorder with broad variation in disease severity arising from different types of intestinal resection. The spectrum of malabsorption ranges from intestinal insufficiency to intestinal failure. Individualized patient strategies involving modifications of dietary macro- and micronutrients, fluid, and pharmacologic options are required to maximize health and quality-of-life outcomes and to minimize complications and SBS-associated mortality.

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Background & Aims: Patients with chronic pancreatitis may be at high risk for osteoporosis and osteopenia. We performed a systematic review and meta-analysis to determine the prevalence of osteoporosis and osteopenia in patients with chronic pancreatitis.

Methods: Articles were identified from MEDLINE, EMBASE, and SCOPUS databases (through October 2012) and a manual search of the literature.

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Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis.

Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer.

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Background & Aims: Although home parenteral nutrition (PN) can save the lives of patients with massive bowel loss that results in short-bowel syndrome and intestinal failure, quality of life is impaired by PN and its complications. We examined the 12-month tolerability and efficacy of teduglutide to reduce PN dependency.

Methods: Patients who received teduglutide (0.

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Background & Aims: Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intestinal failure (SBS-IF). We performed a prospective study to determine whether teduglutide reduces parenteral support in patients with SBS-IF.

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Aim: To determine tolerance to fiber supplementation of semi-elemental tube feeds in critically ill patients and measure its effect on colonic microbiota and fermentation.

Methods: Thirteen intensive care unit patients receiving jejunal feeding with a semi-elemental diet for predominantly necrotizing pancreatitis were studied. The study was divided into 2 parts: first, short-term (3-9 d) clinical tolerance and colonic fermentation as assessed by fecal short chain fatty acid (SCFA) concentrations and breath hydrogen and methane was measured in response to progressive fiber supplementation increasing from 4 g tid up to normal requirement levels of 8 g tid; second, 4 patients with diarrhea were studied for 2-5 wk with maximal supplementation to additionally assess its influence on fecal microbiota quantitated by quantitative polymerase chain reaction (qPCR) of microbial 16S rRNA genes and Human Intestinal Tract Chip (HITChip) microarray analysis.

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