Influence of obesity and related metabolic alterations on colorectal cancer risk

Obesity and related metabolic alterations have been implicated to play a role in colorectal cancer risk. The metabolic syndrome, as assessed according to current international definitions by the key components, abdominal obesity, dyslipidemia, elevated blood pressure, and abnormal glucose metabolism, is associated with colorectal cancer. Recent studies suggest that abdominal obesity and abnormal glucose metabolism may primarily account for this association. Visceral adipose tissue is physiologically more active than subcutaneous adipose tissue and generates hormones and cytokines with inflammatory, metabolic, and direct carcinogenic potential, which may directly or indirectly increase colorectal cancer risk. Current evidence suggests that obesity acts as a risk factor for colorectal cancer by several mechanisms, including chronic low-grade inflammation, hyperinsulinemia, as well as alterations in insulin-like growth factor and adipokine concentrations. Metabolic biomarkers reflecting these processes may not only provide clues for etiological understanding of colorectal carcinogenesis but also might be an alternative way to define an "obesity phenotype" that is relevant for colorectal cancer development

Adipositas und Krebs [Obesity and risk of cancer]

There is growing scientific evidence that overweight and obesity are associated with increased risk of cancer. So far, there is convincing evidence from epidemiological studies that obesity is associated with a higher risk of colorectal cancer, postmenopausal breast cancer, endometrial cancer, renal cell cancer, esophageal adenocarcinoma and pancreatic cancer. A 5 unit increase in body mass index is associated with a 12 % to 51 % higher risk. Abdominal obesity is associated with esophageal adenocarcinoma and colorectal cancer beyond body mass index. Obesity has also been associated with a higher risk of liver and ovarian cancer, although supporting data is less abundant. The mechanisms underlying the positive association between obesity and risk of certain cancers have not been fully elucidated and differ by cancer site. Among the most important potential mechanisms are components of the metabolic syndrome, in particular insulin resistance and hyperinsulinemia, chronic inflammatory processes, sex steroid hormones as well as cytokines secreted by adipose tissue, including leptin and adiponectin

Intake of meat mutagens and risk of prostate cancer in a cohort of U.S. health professionals

BACKGROUND: Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent Methods: In a large US cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity index (MDM) were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. RESULTS: Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR=1.18, 95% CI 1.03-1.35), but not other HCAs (MeIQx, 1.12, 0.98-1.27, PhIP from white meat, 1.07, 0.94-1.21, DiMeIQx, 1.09, 0.97-1.21) or MDM (1.13, 1.00-1.28). For high grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n=483 cases) and advanced cancers (n=281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR=1.44, 95% CI 1.04-1.98, p-trend=0.03; advanced: HR=1.50, 95% 0.99-2.26; p-trend=0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed or processed red meat intake. CONCLUSION: Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer need to be confirmed in other studies. IMPACT: Results do not provide strong evidence that HCAs increase risk of prostate cancers

Gut Microbiome Composition in Obese and Non-Obese Persons: A Systematic Review and Meta-Analysis

Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12, I2 = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, I2 = 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20, I2 = 86%). At the genus level, lower relative proportions of Bifidobacterium and Eggerthella and higher Acidaminococcus, Anaerococcus, Catenibacterium, Dialister, Dorea, Escherichia-Shigella, Eubacterium, Fusobacterium, Megasphera, Prevotella, Roseburia, Streptococcus, and Sutterella were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers

Dietary patterns during high school and risk of colorectal adenoma in a cohort of middle-aged women

Adolescent diet may be etiologically relevant for later risk of colorectal adenoma, a precursor of colorectal cancer. We aimed to examine associations between adolescent dietary patterns (derived using factor analysis) and risk of colorectal adenoma in middle adulthood. We analyzed data from 17,221 women participating in the Nurses' Health Study II, who had completed a validated high school (HS) food frequency questionnaire in 1998 when they were 34-51 years old, and had subsequently undergone at least one lower bowel endoscopy. Between 1998 and 2007, 1,299 women were diagnosed with at least one colorectal adenoma. In multivariable models adjusted for adult dietary patterns, a higher "prudent" pattern during HS, characterized by high consumption of vegetables, fruit and fish was associated with a statistically significantly lower risk of rectal (odds ratio [OR] highest vs. lowest quintile, 0.45, 95% CI 0.27-0.75, p-trend=0.005), but not colon adenomas. A higher "Western" pattern during HS, characterized by high consumption of desserts and sweets, snack foods and red and processed meat, was significantly associated with rectal (OR 1.78, 95% CI 1.12-2.85, p-trend=0.005) and advanced (OR 1.58, 95% CI 1.07-2.33, p-trend=0.08), but not associated with colon or non-advanced adenomas. This study suggests that overall eating patterns during high school may influence later risk of rectal and advanced adenoma, independent of adult diet. Our results support the hypothesis that diet during early life may influence colorectal carcinogenesis

Gut microbiome composition in obese and non-obese persons: a systematic review and meta-analysis

Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (−0.06, 95% CI −0.24, 0.12, I(2) = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, I(2) = 81%) and non-significantly lower Bacteroidetes (−4.79, 95% CI −10.77, 1.20, I(2) = 86%). At the genus level, lower relative proportions of Bifidobacterium and Eggerthella and higher Acidaminococcus, Anaerococcus, Catenibacterium, Dialister, Dorea, Escherichia-Shigella, Eubacterium, Fusobacterium, Megasphera, Prevotella, Roseburia, Streptococcus, and Sutterella were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers

Separation of Oligosaccharides from Lotus Seeds via Medium-pressure Liquid Chromatography Coupled with ELSD and DAD

peer-reviewedLotus seeds were identified by the Ministry of Public Health of China as both food and medicine. One general function of lotus seeds is to improve intestinal health. However, to date, studies evaluating the relationship between bioactive compounds in lotus seeds and the physiological activity of the intestine are limited. In the present study, by using medium pressure liquid chromatography coupled with evaporative light-scattering detector and diode-array detector, five oligosaccharides were isolated and their structures were further characterized by electrospray ionization-mass spectrometry and gas chromatography-mass spectrometry. In vitro testing determined that LOS3-1 and LOS4 elicited relatively good proliferative effects on Lactobacillus delbrueckii subsp. bulgaricus. These results indicated a structure-function relationship between the physiological activity of oligosaccharides in lotus seeds and the number of probiotics applied, thus providing room for improvement of this particular feature. Intestinal probiotics may potentially become a new effective drug target for the regulation of immunity

Obesity, colorectal cancer and MACC1 expression: a possible novel molecular association

Obesity is a major and increasing public health concern, associated with an increased risk of and mortality from several types of cancer including colorectal cancer (CRC), being associated with cancer progression, metastasis and resistance to therapy. It was hypothesized that the expression of cancer/metastasis‑inducing gene metastasis‑associated in colon cancer 1 (MACC1) is increased in obesity, which may constitute a link to obesity‑induced cancer. The present study thus analyzed circulating cell‑free plasma MACC1 expression levels in human obese (vs. normal weight) adult individuals from independent studies, namely the Martin Luther University (MLU) study (n=32) and the Metabolic syndrome study (MetScan, Berlin) (n=191). Higher plasma MACC1 levels were found in obese individuals, increasing with a greater body fat mass and body mass index; these levels were predominantly observed in male and to a lesser extent in female individuals, although the results were not significant. A reduction in body fat mass following dietary intervention and physical exercise decreased the MACC1 expression levels in the MLU study. Furthermore, Wistar rats with diet‑induced obesity exhibited slightly increased plasma MACC1 levels compared with rats of normal weight. The obese Wistar rats exposed to azoxymethane to induce colon cancer exhibited a more severe colon tumor outcome, which was associated with significantly increased MACC1 levels compared with their non‑obese littermates. On the whole, the findings of the present study suggest an association between MACC1 and obesity, as well as with obesity‑induced CRC

ONS : an ontology for a standardized description of interventions and observational studies in nutrition

Background: The multidisciplinary nature of nutrition research is one of its main strengths. At the same time, however, it presents a major obstacle to integrate data analysis, especially for the terminological and semantic interpretations that specific research fields or communities are used to. To date, a proper ontology to structure and formalize the concepts used for the description of nutritional studies is still lacking. Results: We have developed the Ontology for Nutritional Studies (ONS) by harmonizing selected pre-existing de facto ontologies with novel health and nutritional terminology classifications. The ONS is the result of a scholarly consensus of 51 research centers in nine European countries. The ontology classes and relations are commonly encountered while conducting, storing, harmonizing, integrating, describing, and searching nutritional studies. The ONS facilitates the description and specification of complex nutritional studies as demonstrated with two application scenarios. Conclusions: The ONS is the first systematic effort to provide a solid and extensible formal ontology framework for nutritional studies. Integration of new information can be easily achieved by the addition of extra modules (i.e., nutrigenomics, metabolomics, nutrikinetics, and quality appraisal). The ONS provides a unified and standardized terminology for nutritional studies as a resource for nutrition researchers who might not necessarily be familiar with ontologies and standardization concepts

Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers