Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.
Purpose: Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood. Methods: We conducted a case–control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann–Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence. Results: The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11–0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus. Conclusions: The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.
Flavonoids have been inversely associated to colorectal cancer (CRC) and are plausible intermediaries for the relation among gut microbiome, intestinal permeability and CRC. We analyzed the relation of flavonoid intake with CRC and blood bacterial DNA. We conducted a case–control study in Italy involving 100 incident CRC cases and 200 controls. A valid and reproducible food–frequency questionnaire was used to assess dietary habits and to estimate six flavonoid subclass intakes. We applied qPCR and 16S rRNA gene profiling to assess blood bacterial DNA. We used multiple logistic regression to derive odds ratios (ORs) of CRC and Mann–Whitney and chi-–square tests to evaluate abundance and prevalence of operational taxonomic units (OTUs) according to flavonoid intakes. Inverse associations with CRC were found for anthocyanidins (OR for the highest versus the lowest tertile = 0.24, 95% confidence interval, CI = 0.11–0.52) and flavanones (OR = 0.18, 95% CI = 0.08–0.42). We found different abundance and prevalence according to anthocyanidin and flavanone intake for OTUs referring to Oligoflexales order, Diplorickettsiaceae family, Staphylococcus, Brevundimonas, Pelomonas and Escherischia–Shigella genera, and Flavobacterium and Legionella species. The study provides evidence to a protective effect of dietary anthocyanidins and flavanones on CRC and suggests an influence of flavonoids on blood bacterial DNA, possibly through intestinal permeability changes.
Frailty is a geriatric syndrome that results from multisystem impairment caused by age‐associated accumulation of deficits. The frailty index is used to define the level of frailty. Several studies have searched for molecular biomarkers associated with frailty, to meet the needs for personalized care. Cyclase‐associated protein 2 (CAP2) is a multifunctional actin‐binding protein involved in various physiological and pathological processes, that might reflect frailty's intrinsic complexity. This study aimed to investigate the association between frailty index and circulating CAP2 concentration in 467 community‐dwelling older adults (median age: 79; range: 65–92 years) from Milan, Italy. The selected robust regression model showed that circulating CAP2 concentration was not associated with chronological age, as well as sex and education. However, circulating CAP2 concentration was significantly and inversely associated with the frailty index: a 0.1‐unit increase in frailty index leads to ~0.5‐point mean decrease in CAP2 concentration. Furthermore, mean CAP2 concentration was significantly lower in frail participants (i.e., frailty index ≥0.25) than in non‐frail participants. This study shows the association between serum CAP2 concentration and frailty status for the first time, highlighting the potential of CAP2 as a biomarker for age‐associated accumulation of deficits.
Serum vitamin D (VitD) levels have been inversely related with metabolic syndrome (MetS), although the direct impact of VitD is still debated. This study examined 879 subjects of working age from an obesity and occupational clinic in Milan, Italy. Among these participants, 316 had MetS, while 563 did not. A multiple logistic regression analysis was conducted to determine the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for MetS in relation to serum VitD levels. After controlling for age, sex, leisure time physical activity, and body mass index (BMI), individuals with VitD levels between 20 and 29.9 ng/dL, or at least 30 ng/dL, had approximately half the risk of developing MetS (OR: 0.52, 95% CI: 0.32–0.86 and OR: 0.50, 95% CI: 0.25–0.99, respectively) compared to those with VitD levels below 10 ng/dL. This study presents further evidence of the beneficial effect of adequate VitD levels on the risk of MetS in a population of overweight/obese workers, even after adjusting for BMI. This study supports the importance of testing for and—if required—supplementing VitD in individuals with metabolic risk factors.
To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of −0.70 for the DAS28-CRP, and −3.6 for the SDAI (overall analysis) and of −1.10 and −5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity.