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A systematic review and meta-analysis of diet and nutrient intake in adults with irritable bowel syndrome.
Veraza, DI, Calderon, G, Jansson-Knodell, C, Aljaras, R, Foster, ED, Xu, H, Biruete, A, Shin, A
Neurogastroenterology and motility. 2024;(1):e14698
Abstract
BACKGROUND Numerous individual and environmental factors including diet may play an important role in the pathophysiology of irritable bowel syndrome (IBS). It is unclear to what degree dietary intake is affected in individuals with IBS. We aimed to perform a systematic review and meta-analysis to summarize dietary intake of adults with IBS and to compare dietary intake between adults with IBS and non-IBS controls. METHODS Ovid MEDLINE, Embase, Cochrane, CINAHL, and Scopus were searched through February 2023 for clinical trials and observational studies measuring usual diet in adults with IBS. Pooled weighted averages were estimated for total energy, macronutrient, and micronutrient data. Mean differences (MD) in nutrient intake were estimated for adults with IBS versus non-IBS controls using a random effects model. Heterogeneity was assessed by the inconsistency index (I2). KEY RESULTS Sixty-three full-text articles were included in the review of which 29 studies included both IBS and control subjects. Nutrients not meeting the recommended intake level for any dietary reference values in the IBS population were fiber and vitamin D. Meta-regression by female proportion was positively correlated with total fat intake and negatively correlated with carbohydrate intake. Comparisons between participants with IBS and controls showed significantly lower fiber intake in participants with IBS with high heterogeneity (MD: -1.8; 95% CI: -3.0, -0.6; I2 = 85%). CONCLUSIONS AND INFERENCES This review suggests that fiber and vitamin D intake is suboptimal in IBS; however, overall dietary intake does not appear to be comprised. Causes and consequences of reduced fiber in IBS deserve further study. Results of this systematic review and meta-analysis suggest that fiber and vitamin D intake is suboptimal in IBS. However, overall intake of other macro- and micronutrients does not appear to be compromised. Causes and consequences of reduced fiber and Vitamin D intake in IBS deserve further study.
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Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.
Yin, X, Kishida, R, Abe, SK, Islam, MR, Rahman, MS, Saito, E, Lan, Q, Blechter, B, Merritt, M, Choi, JY, et al
International journal of cancer. 2024;(12):2090-2105
Abstract
Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.
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Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.
Oze, I, Ito, H, Koyanagi, YN, Abe, SK, Rahman, MS, Islam, MR, Saito, E, Gupta, PC, Sawada, N, Tamakoshi, A, et al
International journal of cancer. 2024;(7):1174-1190
Abstract
Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.
Fernandez-Rozadilla, C, Timofeeva, M, Chen, Z, Law, P, Thomas, M, Schmit, S, Díez-Obrero, V, Hsu, L, Fernandez-Tajes, J, Palles, C, et al
Nature genetics. 2023;(1):89-99
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Abstract
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
Thomas, M, Su, YR, Rosenthal, EA, Sakoda, LC, Schmit, SL, Timofeeva, MN, Chen, Z, Fernandez-Rozadilla, C, Law, PJ, Murphy, N, et al
Nature communications. 2023;(1):6147
Abstract
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome.
Waseem, MR, Shin, A, Siwiec, R, James-Stevenson, T, Bohm, M, Rogers, N, Wo, J, Waseem, L, Gupta, A, Jarrett, M, et al
Clinical and translational gastroenterology. 2023;(1):e00541
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Abstract
INTRODUCTION Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.
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Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.
Fernandez-Rozadilla, C, Timofeeva, M, Chen, Z, Law, P, Thomas, M, Schmit, S, Díez-Obrero, V, Hsu, L, Fernandez-Tajes, J, Palles, C, et al
Nature genetics. 2023;(3):519-520
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Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults.
Jansson-Knodell, CL, Krajicek, EJ, Ramakrishnan, M, Rogers, NA, Siwiec, R, Bohm, M, Nowak, T, Wo, J, Lockett, C, Xu, H, et al
Digestive diseases and sciences. 2022;(12):5617-5627
Abstract
BACKGROUND Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. AIMS We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. METHODS Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. RESULTS Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). CONCLUSIONS Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.
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Faecal incontinence in adults.
Bharucha, AE, Knowles, CH, Mack, I, Malcolm, A, Oblizajek, N, Rao, S, Scott, SM, Shin, A, Enck, P
Nature reviews. Disease primers. 2022;(1):53
Abstract
Faecal incontinence, which is defined by the unintentional loss of solid or liquid stool, has a worldwide prevalence of ≤7% in community-dwelling adults and can markedly impair quality of life. Nonetheless, many patients might not volunteer the symptom owing to embarrassment. Bowel disturbances, particularly diarrhoea, anal sphincter trauma (obstetrical injury or previous surgery), rectal urgency and burden of chronic illness are the main risk factors for faecal incontinence; others include neurological disorders, inflammatory bowel disease and pelvic floor anatomical disturbances. Faecal incontinence is classified by its type (urge, passive or combined), aetiology (anorectal disturbance, bowel symptoms or both) and severity, which is derived from the frequency, volume, consistency and nature (urge or passive) of stool leakage. Guided by the clinical features, diagnostic tests and therapies are implemented stepwise. When simple measures (for example, bowel modifiers such as fibre supplements, laxatives and anti-diarrhoeal agents) fail, anorectal manometry and other tests (endoanal imaging, defecography, rectal compliance and sensation, and anal neurophysiological tests) are performed as necessary. Non-surgical options (diet and lifestyle modification, behavioural measures, including biofeedback therapy, pharmacotherapy for constipation or diarrhoea, and anal or vaginal barrier devices) are often effective, especially in patients with mild faecal incontinence. Thereafter, perianal bulking agents, sacral neuromodulation and other surgeries may be considered when necessary.
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Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk.
Shu, X, Chen, Z, Long, J, Guo, X, Yang, Y, Qu, C, Ahn, YO, Cai, Q, Casey, G, Gruber, SB, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022;(6):1216-1226
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Abstract
BACKGROUND The etiology of colorectal cancer is not fully understood. METHODS Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis. RESULTS Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60-2.36, P = 2.6 × 10-11; OREUR 1.01, 95% CI, 0.99-1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer. CONCLUSIONS This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data. IMPACT The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.