Data_Sheet_1_A 1 year course of starch- and sucrose-reduced diet used by irritable bowel syndrome patients with diarrhoea and the effect of genetic variants.PDF

BackgroundIrritable bowel syndrome is a heterogeneous syndrome and it is difficult to find an effective treatment. Previously, a starch- and sucrose-reduced diet (SSRD) demonstrated promising short-term outcomes. It was proposed that genetic variants in the sucrose-isomaltase gene might influence this success. Our aim in this work was to extend the follow-up study to 1 year and to analyse the effect of the genetic variants of genes involved in starch and sucrose metabolism.MethodsIBS-SSS questionnaire, IBS-QoL questionnaire and questionnaires about adherence, difficulty and food assessment were sent to 34 patients after 6 months and 1 year after the end of the dietary intervention. In addition, 11 genes involved in sucrose and starch metabolism were sequenced.ResultsTwenty-three participants responded to the 6 months follow-up and 16 to the 1 year follow-up. IBS-SSS total value increased 59.71% in the 6 months follow-up compared with the end of the intervention (p = 0.0018), and 55.39% in the 1 year follow-up (p = 0.0166); while IBS-QoL score decreased 24.09% (p = 0.0002) and 18.07% (p = 0.0022), respectively. The adherence decreased by 29.11% (p = 4.8 × 10−5) and 27.21% (p = 0.0054), respectively. In addition, carriers of pathogenic variants on the SI gene showed a slightly better performance than non-carriers. Finally, the participants showed less satisfaction over time with 18 allowed foods in the diet.ConclusionOver time the SSRD is difficult to follow and the genotype might affect the performance of the diet. Since this diet could be a promising therapeutic option, a larger cohort needs to be analysed to validate the results and to compare it with other diets.</p

Data_Sheet_1_A 1 year course of starch- and sucrose-reduced diet used by irritable bowel syndrome patients with diarrhoea and the effect of genetic variants.PDF

BackgroundIrritable bowel syndrome is a heterogeneous syndrome and it is difficult to find an effective treatment. Previously, a starch- and sucrose-reduced diet (SSRD) demonstrated promising short-term outcomes. It was proposed that genetic variants in the sucrose-isomaltase gene might influence this success. Our aim in this work was to extend the follow-up study to 1 year and to analyse the effect of the genetic variants of genes involved in starch and sucrose metabolism.MethodsIBS-SSS questionnaire, IBS-QoL questionnaire and questionnaires about adherence, difficulty and food assessment were sent to 34 patients after 6 months and 1 year after the end of the dietary intervention. In addition, 11 genes involved in sucrose and starch metabolism were sequenced.ResultsTwenty-three participants responded to the 6 months follow-up and 16 to the 1 year follow-up. IBS-SSS total value increased 59.71% in the 6 months follow-up compared with the end of the intervention (p = 0.0018), and 55.39% in the 1 year follow-up (p = 0.0166); while IBS-QoL score decreased 24.09% (p = 0.0002) and 18.07% (p = 0.0022), respectively. The adherence decreased by 29.11% (p = 4.8 × 10−5) and 27.21% (p = 0.0054), respectively. In addition, carriers of pathogenic variants on the SI gene showed a slightly better performance than non-carriers. Finally, the participants showed less satisfaction over time with 18 allowed foods in the diet.ConclusionOver time the SSRD is difficult to follow and the genotype might affect the performance of the diet. Since this diet could be a promising therapeutic option, a larger cohort needs to be analysed to validate the results and to compare it with other diets.</p

Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

<div><h3>Background</h3><p>Colorectal cancer (CRC) is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool.</p> <h3>Aim</h3><p>Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC.</p> <h3>Methods</h3><p>In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF), cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2), and CD44) and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA) and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results.</p> <h3>Results</h3><p>Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79±0.25 in the CRC group vs 1.27±0.25 in the control group, P<0.0005). The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79–0.96). The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81) and tetranectin (0.80), COX-2 (0.78), uPAR (0.78) and carbonic anhydrase (0.77). The markers which identified early stage CRC (Stages I and II) were alpha 1-antitrypsin, uPAR, COX-2 and MMP7.</p> <h3>Conclusions</h3><p>Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages.</p> </div

The areas under ROC curve for all the mRNA expression levels analysed in blood.

<p>PAI; plasminogen activator inhibitor MMP7;matrix metalloproteinase 7 uPAR; urokinase-type plasminogen activator receptor uPA;urokinase-type plasminogen activator VEGF; vascular endothelial growth factor COX-2; cyclooxygenase 2.</p

ROC curves comparing carcinoembrionic antigen (CEA) in serum and MMP7 RNA expression.

<p>The areas under ROC curve for CEA and matrix metalloproteinase 7 (MMP7) were 0.84 and 0.81, respectively.</p

The levels of mRNA expression of the proteins analysed and the statistical significance of differences in the values between cancer tissue and healthy tissue in patients with CRC.

<p>SD; standard deviation PAI; plasminogen activator inhibitor MMP7;matrix metalloproteinase 7 uPAR; urokinase-type plasminogen activator receptor uPA;urokinase-type plasminogen activator VEGF; vascular endothelial growth factor COX-2; cyclooxygenase 2.</p

The levels of mRNA expression in blood of the proteins analysed and the statistical significance of differences in the values between patients with CRC and controls.

<p>SD; standard deviation PAI; plasminogen activator inhibitor MMP7;matrix metalloproteinase 7 uPAR; urokinase-type plasminogen activator receptor uPA;urokinase-type plasminogen activator VEGF; vascular endothelial growth factor COX-2; cyclooxygenase 2.</p

The results shown are the levels of alpha1 antitrypsin, tetranectin, COX-2 and matrix metalloproteinase 7 (MMP7) for the healthy individuals and patients with colorectal cancer.

<p>The cutoff corresponds with highest accuracy (minimal false negative and false positive). Shows the sensitivity and specificity for the cutoff with highest accuracy.</p

Oligonucleotide primer sequences generated used for the detection of mRNA for CRC markers.

<p>Oligonucleotide primer sequences generated used for the detection of mRNA for CRC markers.</p

Data_Sheet_1_Identification of taxonomic changes in the fecal bacteriome associated with colorectal polyps and cancer: potential biomarkers for early diagnosis.CSV

Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota. Host-related factors and inherent characteristics of polyps and tumors may contribute to microbiome variability, potentially acting as confounding factors in the discovery of taxonomic biomarkers for both conditions. In this study we employed shotgun metagenomics to analyze the taxonomic diversity of bacteria present in fecal samples of 90 clinical subjects (comprising 30 CRC patients, 30 with polyps and 30 controls). Our findings revealed a decrease in taxonomic richness among individuals with polyps and CRC, with significant dissimilarities observed among the study groups. We identified significant alterations in the abundance of specific taxa associated with polyps (Streptococcaceae, Lachnoclostridium, and Ralstonia) and CRC (Lactobacillales, Clostridiaceae, Desulfovibrio, SFB, Ruminococcus, and Faecalibacterium). Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, our study revealed a positive co-occurrence among underrepresented genera in CRC, while demonstrating a negative co-occurrence between Faecalibacterium and Desulfovibrio, suggesting potential antagonistic relationships. Moreover, we observed variations in taxonomic richness and/or abundance within the polyp and CRC bacteriome linked to polyp size, tumor stage, dyslipidemia, diabetes with metformin use, sex, age, and family history of CRC. These findings provide potential new biomarkers to enhance early CRC diagnosis while also demonstrating how intrinsic host factors contribute to establishing a heterogeneous microbiome in patients with CRC and polyps.</p