Janaina Lombello Santos Donadio

Introduction: Growing evidence suggests that the gut microbiota, mainly modulated by diet, is involved in CRC development. Pectins, a class of highly fermentable dietary fibers, can modulate the gut microbiota which depends upon the ripening stages of the fruit. Objective: This work aimed to investigate the differential effects of ripe and unripe papaya pectins on gut microbiota composition in a mouse model of colon carcinogenesis. Methods: Male Wistar rats were divided into 4 groups fed ripe and unripe papaya pectins and subjected to AOM injections. Animals were euthanized after 10 weeks. Aberrant crypt focus (ACF) and SCFA production were analyzed in the colon. Metagenomic sequencing was done using Nanopore sequencing technology. The AOM model is known to increase the infiltration of neutrophils and M2 macrophages in the tumor microenvironment, as well as decrease the cytotoxixity of CD8+T cells and increase the Tregs in the tumor microenvironment, contributing to tumor growth. Results: Ripe papaya pectin intake reduced the number of ACF with 1 and 2 crypts. Acetate production was higher in animals fed ripe and unripe papaya pectin. Ripe papaya pectin increased richness in microbiota alpha diversity. The ripe papaya pectin group and the negative control group shared a similar bacterial profile. The intake of ripe papaya pectin increased the abundance of Lactobacillus and Limosilactobacillus while the intake of ripe papaya pectins increased the abundance of Rombutsia. The AOM experimental group had an increase in the abundance of Mediterraneibacter. The lactobacillus especially is known to interat Conclusion: These results suggest that the intake of ripe papaya pectin had a potential preventive effect on colon carcinogenesis development by decreasing the number of ACF, increasing SCFA production, and increasing the abundance of Lactobacillus, a well-known probiotic strain that promotes health benefits to the host. This could be beneficial in future preventive measures to reduce CRC development using a natural component of the diet rich in dietary fiber. Supported by the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.01.01/00/22_008/0004597) CRC: colorectal cancer, AOM: azoxymethane, SCFA: short chain fatty acids, ACF: aberrant crypt focus.

Diet shapes the tumor microenvironment in colorectal cancer by modulating the reactivity of the immune system. We investigated the immunomodulatory properties of increased dietary protein intake in the early phase of tumorigenesis in a mouse model of colitis-associated cancer. BALB/c mice were fed a synthetic control diet (CD) or a high-protein diet (HPD) and subsequently treated with azoxymethane and dextran sodium sulfate to induce colitis-associated cancer. The involvement of macrophages in tumorigenesis was examined by depleting them with clodronate-loaded liposomes. Immunophenotyping was performed by flow cytometry, and cytokine production in Peyer’s patches (PPs) was measured by ELISA. Colonoscopic screening was performed to assess tumor characteristics. HPD-fed mice developed more numerous and larger tumors and had a lower proportion of systemic CD8+ T cells. However, clodronate-mediated depletion of macrophages during early tumorigenesis significantly reduced tumor incidence and restored CD8+ T cells. In the spleens of clodronate-treated mice, a proinflammatory macrophage subpopulation was partially depleted, along with a significant reduction in neutrophils, while NK, NKT and DC cells increased. In addition, HPD-fed mice had elevated proinflammatory TNFα, IL-17, IL-1β and S100A8 in PPs, with TNFα and IL-17 even higher in clodronate-untreated mice. Our findings demonstrated that HPD contributes to intestinal inflammation and exacerbates tumor development driven either by macrophage or neutrophil stimulation. This study was supported by the Czech Academy of Sciences (LQ200202105) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.01.01/00/22_008/0004597).

The gut microbiota is essential in human health, influencing various physiological processes ranging from digestion and metabolism to immune function and mental health.

The intake of dietary fibers has been associated with a reduction in the risk of colorectal cancer.

Selenium (Se) is an essential micronutrient for human biology that executes its functions as the amino acid selenocysteine via selenoproteins, which have important functions in, for example, antioxidation, immunomodulation, thyroid metabolism, and human fertility. Se nutritional status is assessed using the quantification of blood Se biomarkers, which are influenced by several factors, including diet, age, gender, smoking status, alcohol consumption, health condition, and the genetic characteristics of individuals. Nutrigenetic studies have identified single nucleotide polymorphisms in selenoproteins that might clarify the high variability in values reported for biomarkers of Se nutritional status in different populations, and the response of these biomarkers to Se supplementation with either organic or inorganic forms of Se. This review aims to (1) define the basic aspects of Se biology, (2) describe the current most commonly used biomarkers of Se nutritional status, and (3) provide a summary of associations between functional single nucleotide polymorphisms in selenoproteins and biomarkers of Se status in healthy populations.

Background: NKX3.1 is a tumor suppressor frequently lost in prostate cancer. Previous studies by others indicated that the risks associated with reduced NKX3.1 levels can be enhanced by anti‐oxidant supplementation. Selenium is an essential component of several proteins with anti‐oxidant functions and lower levels of selenium have been associated with greater risk of prostate cancer. In contrast, participants of the select prostate cancer prevention trial were at increased risk of prostate cancer when supplemented with selenium when their baseline selenium levels were high.Methods: In order to investigate whether there was an interaction between a functional polymorphism in NKX3.1 that results in less protein and selenium status with prostate cancer grade or outcome, plasma selenium levels and the genotypes of NKX3.1 and the selenium carrier protein SELENOP were determined from a cohort of men who underwent radical protatectomy.Results: NKX3.1 and SELENOP genotypes were associated with a more aggressive prostate tumor grade at the time of prostatectomy, but there were no significant interactions of NKX3.1 genotype with either selenium status or SELENOP genotype. There was also a significant association between NKX3.1 genotype and prostate cancer recurrence, however this association was modified by SELENOP genotype, but not with plasma selenium levels.Conclusions: These data indicate that the impact of selenium status on prostate cancer may be influenced by factors other than the amount of selenium in circulation.

Selenium (Se) is an essential micronutrient for human health. Its beneficial effects are exerted by selenoproteins, which can be quantified in blood and used as molecular biomarkers of Se status. We hypothesize that the presence of genetic polymorphisms in selenoprotein genes may: (1) influence the gene expression of specific selenoproteins and (2) influence the pattern of global gene expression after Brazil nut supplementation. The study was conducted with 130 healthy volunteers in Sao Paulo, Brazil, who consumed one Brazil nut (300 μg/Se) a day for eight weeks. Gene expression of GPX1 and SELENOP and genotyping were measured by real-time PCR using TaqMan Assays. Global gene expression was assessed by microarray using Illumina HumanHT-12 v4 BeadChips. Brazil nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450 (p < 0.05). SELENOP mRNA expression was significantly higher in A-carriers at rs7579 either before or after supplementation (p < 0.05). Genotype for rs713041 in GPX4 affected the pattern of blood cell global gene expression. Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP selenoprotein gene expression and global gene expression in response to Brazil nut supplementation.

Purpose The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults. Methods The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins. Results The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053). Conclusions Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.

Selenium (Se) status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the association between SNPs in glutathione peroxidase genes and biomarkers of Se status in healthy Brazilians. The study was conducted in 116 healthy adults in São Paulo, Brazil. Plasma and erythrocyte Se were measured by HGFAAS. Erythrocyte GPx (eGPx) activity was measured spectrometrically in a biochemical analyzer. Genotypes were determined by real-time PCR using Taqman^® Assays. eGPx activity was higher in females compared with males. Lower erythrocyte Se concentrations were found in heterozygous GC carriers for GPX1 rs8179169. eGPx activity was higher in females with the common genotypes, except for rs8179169. GC carriers for rs8179169 had lower erythrocyte Se in both genders, and only male carriers of the variant alleles of both rs1050450 and rs1800668 had higher eGPx activity. In conclusion, the genotype for SNPs in GPX1 and gender affected biomarkers of Se status in this pilot study with healthy Brazilians.