It is of the utmost importance to identify interventions that are both effective and economically feasible bearing in mind the high rates of non-communicable diseases associated with inadequate nutrition around the globe and projections of greater rate increases in low- and middle-income countries. An increasing number of modeling studies indicate that population-wide strategies may have greater and longer-lasting benefits for population health at a lower cost to society. Personalized nutrition has attracted a lot of attention recently since it might help to prevent diet-related diseases more effectively and efficiently. However, to the best of our knowledge, there hasn't been a thorough analysis of the cost-effectiveness of interventions that include a personalized nutrition component. Thus, in our presentation, a critical analysis and a sneak peek at the methodology and findings of a previously published very diverse body of literature on cost-effectiveness evaluations of interventions with a personalized nutrition component will be given. There is heterogeneity in the cost-effectiveness analyses methodology used in the personalized nutrition field, including disparities in definitions and conceptualization, PICOs, and modeling approaches. All things considered, regardless of differences in health economic outcomes within studies, interventions with a personalized nutrition component are in general more economical than a one-size-fits-all strategy. Lastly, the best way to further increase health outcomes and cost-effectiveness is through an integrated strategy that incorporates both psychological and biological concepts of individualization.

Objectives: We have previously shown that inhibition of the mTORC1 nutrient-sensing complex by rapamycin and mTORC1/mTORC2 Inhibition by either Torin-2 or RapaLink-1 have differential effects on the global untargeted metabolomics in vivo and in vitro cell culture models.

Methods: In this study, we leveraged the mummichog Python algorithm to analyze the high-dimension untargeted metabolomics data to model the biochemical pathways and metabolic networks and predict their functional activity. We used pancreatic beta-cell culture (Beta TC6) and incubated the cells with either Rapalink-1, rapamycin or the vehicle control for 24 hours. Cells were harvested and snap-frozen in liquid nitrogen. Cells were extracted in ethanol, and the supernatant was collected. The untargeted metabolomics was performed using the high-resolution mass spectrometry LC-MS/MS HILIC peak detection of ESI positive and negative polarity modes. The data were collected using Bruker's maXis-II ESI-Q-q-TOF coupled to Dionex Ultimate-3000 U(H)PLC system using Sequant ZIC-HILIC 150x2.1 mm column (Bruker, Hamburg, Germany). We compared the HRMS-based untargeted precision metabolomics (LC-MS/MS) between groups using positive and negative polarity modes to capture both hydrophilic and hydrophobic metabolites. We employed the XCMS plus bioinformatics platform to link mTOR-regulated metabolites to the predicted biological pathways using the mummichog Python algorithm. Statistical significance (p< 0.001) was assessed by ANOVA and Ranked order data by Whitney-Cox followed by ad-hoc unpaired t-test.

Results: The Cluster heatmap deconvolution and cloud plots analysis show the differential pattern of metabolites between rapamycin and Rapalink-treated pancreatic beta cell lines. Mapping the downstream metabolites data onto predictive metabolic pathways and activity networks revealed that the top pathways affected included the pentose phosphate pathway, dopamine and ubiquinol degradation pathways in the ESI positive polarity mode, and creatine synthesis/glycine degradation and nicotine degradation pathways in the ESI negative polarity mode.

Conclusions: The high-resolution untargeted metabolomics can be leveraged as a proxy of the internal exposome yielding high-dimensional data that provide mechanistic insights into metabolic and signaling pathways and the underlying biology. This approach will have beneficial applications of the internal exposome in determining the optimal precision nutrition pathways for personalized medicine.

Funded by PSC-CUNY Grant 54-101 and the City University of New York, GC Advanced Science Research Center Seed Grant Award # 95649-00. XCMS Plus is a platform for analyzing untargeted metabolomics with an integrated METLIN in silico fragmentation tandem MS database.

In recent years, there has been a constant growth in the prevalence of chronic non-communicable diseases, which even appear increasingly at an earlier age. However, there is a close relationship in the development of these diseases after menopause, related to the estrogenic signaling occurring in various tissues; such is the case of the bladder, compromising its physiology in females. Considering that women are more affected by bladder diseases such as urinary incontinence, it is of relevance to analyze the effect of metabolic syndrome (MS) models of diet through cafeteria diet (CAF) or high fat/high sugar diet (HF/HS) on the bladder urothelium of female rats. Eighteen 12-week-old Wistar rats were used. The female rats were divided into an intact control group (C, n=6), a cafeteria diet SMet group (CAF, n=6), and a high-fat/high-sugar diet SMet group (HF/HS, n=6). Control group had access to water and feed (23% protein, 50% carbohydrate, and 27% lipid) ad libitum; the cafeteria group had a designed diet (approximately 11% protein, 60% carbohydrate, and 29% lipid) in which ultra-processed feeds were used, the high-fat/high-sugar diet (HF/HS) was designed and pellets were prepared with a composition of (18% protein, 55% carbohydrate, and 27% lipid). The duration of the treatments was 10 weeks. After treatment, all animals were euthanized and blood was obtained for biochemical evaluations (cholesterol and triglycerides), as well as bladder. Each tissue was stained with Masson's trichrome and PAS, and photographs were taken at 10x, 40x, and 100x. Data were analyzed statistically and differences were considered when P< 0.05, using graph Pad v.6 statistical packages. The cafeteria diet was effective in generating metabolic syndrome, with the presence of hyperglycemia, elevated cholesterol, and triglycerides, as well as excess body weight, while the HF/HS diet generated increased body weight and hyperglycemia, but not dyslipidemia. The effect on the urothelium was differential in each treatment, being more affected with the cafeteria diet. Atrophy and hyperplasia were observed in the case of the CAF diet, while the other scheme only generated inflammatory foci, in the case of the CAF diet there is the presence of fibrosis. The results show that the cafeteria diet is a model that could be more useful to analyze metabolic syndrome in females, compared to other diet-generated models. Further studies are required to analyze the relationship of bladder alterations in females.

Ceballos D ^1,2, Casanova-Crespo S ^1,2, Rodríguez-Lagunas, M.J. ^1,2, Castell, M. ^1,2, Massot-Cladera M ^1,2, Pérez-Cano, F.J. ^1,2

¹Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain

²Institut of Research in Nutrition and Food Safety (INSA-UB), Barcelona, Spain

Author responsible: danielaceballoss@ub.edu

INTRODUCTION AND OBJECTIVES

Maternal diet during lactation, pregnancy or even before can influence the health of the baby; being the Mediterranean diet the one with the highest level of evidence due to its richness in fiber and polyphenols, among other bioactive components.

This study investigated the impact of a diet rich in fiber and polyphenols supplemented during pregestation, gestation, and lactation at intestinal level in both dams and their offspring.

MATERIAL AND METHODS

Two groups of rats were formed, one receiving the experimental diet high in fiber and polyphenols (HFP) and the other serving as the reference diet (REF). Animals received the diet during pregestation (21 days), gestation (21 days), and lactation (21 days). At the end of lactation, organ samples were obtained and evaluated. Among others, the intestine was on the main focus and obtained for weight, size, histology, and immunoglobulin (Ig) A response.

RESULTS AND DISCUSSION

A significant increase in the relative weight of the caecum and small intestine was observed in pregnant rats from the experimental HFP group compared to the REF group (p<0.05). Surprisingly, the offspring from the HFP group also influenced the intestinal weight and exhibited significantly greater length of the small intestine at both 1 and 21 days of life compared to the offspring from the REF group (p<0.05). This trophic effect is not related to a direct intake of the fiber or polyphenols and therefore they could be derived from intrauterine epigenetic changes, the impact of diet on maternal milk composition or microbiota, or a combination of these factors. Future studies will evaluate the mechanisms involved to gain a better understanding of these results.

CONCLUSION

In conclusion, a diet rich in fiber and polyphenols appears to have an intestinal impact in both pregnant rats and their offspring. However, further research is required to elucidate the underlying mechanisms of these effects and their potential implications for maternal and neonatal health.

Not all cancer patients respond to immunotherapy, and the variation in response may be attributed to the individual's microbiome, which is profoundly influenced by dietary habits. Understanding and manipulating the microbiome through dietary interventions offer a potential avenue for enhancing immunotherapy outcomes in cancer patients and consequently may serve as a complementary therapeutic strategy.
Bearing in mind the latter as well as our previous research the importance of gut microbiome as a co-denominator for immunotherapy response, and aiming towards constructing a protocol on dietary intervention for enhancing immunotherapy response in metastatic melanoma patients, we performed a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 2130 citations were identified through searching PubMed/Medline using the following search strategy: ((food) OR (diet*) OR (nutri*)) AND (immunother*) AND ((butyrate) OR (SCFA) OR (microbio*)) AND (cancer). Animal studies, studies with participants younger than 18, review articles, case reports, book chapters and publications before 2015 were not within our scope. Since any relevant investigational studies were not identified, we proceeded with exploring diet-microbiome-immunotherapy axis through hand-searching and analyzing the secondary/indirect evidence.
Different dietary habits can influence the abundance and diversity of microorganisms within the gut. A diet with moderately elevated sodium use (2.3-4 g per day) diet rich in fiber (>25 g daily), fruits and vegetables (≥5 servings daily), and whole grains (≥3 servings daily) has been associated with a more diverse and beneficial microbiome, which in turn promotes the production of short-chain fatty acids (SCFA). On the other hand, a diet high in processed foods, sugars, and saturated fatty acids may lead to a less diverse and potentially less favorable microbiome.
A scarce body of literature, discussing on the intricate interplay between the microbiome and immune system, suggests that specific microbiome signatures producing essential metabolites such as SCFAs may enhance the effectiveness of immunotherapy. To elaborate, SCFAs can regulate the activity of immune cells not only by triggering metabolic and epigenetic reprogramming but also by binding to cognate receptors on the surface of cells.
Thus, profound understanding of the complex relationship between diet, SCFAs, and immunotherapy response holds great promise for developing personalized dietary approaches to cancer immunotherapy-containing treatment regimens. To deduce, by elucidating the mechanisms involved and identifying concrete personalized dietary strategies that optimize gut microbiome and SCFA production, it may be possible to further enhance the effectiveness of immunotherapy, offer novel therapeutic approaches for cancer patients, and improve their quality of life.

CMOs are complex carbohydrates found in cow milk that resemble the oligosaccharides in human milk and are essential for regulating the immune system and forming the gut flora of infants. As prebiotics, they promote the growth of specific beneficial gut bacteria, such as Lactobacilli and Bifidobacteria, which promotes the creation of short-chain fatty acids for gut health. Furthermore, CMOs correlate with enhanced infant immune system development, offering safeguards against pathogens and anti-inflammatory benefits.
The results of recent CMO research are revealed in this review, together with their biological importance and potential applications. Their relevance to infant nutrition is highlighted, as is their potential to be used as bioactive ingredients in novel functional foods and nutraceuticals. The abstract also describes upcoming obstacles and opportunities for CMO research, such as understanding their structures and functions, improving extraction methods, and expanding applications to different age groups.

Introduction: The gut microbiome has been recently put in focus for its implications in the pathogenesis and treatment of melanoma, and together with diet may have an influence on the effectiveness of treatment. Dietary fibre (DF) intake impacts gut microbiome composition and metabolic function but greatly varies across individuals whose response to fibres depends on their baseline gut microbiome. This study aimed to determine microbiome differences among melanoma progression-free survival patients regarding their DF intake.

Methods: Croatian metastatic melanoma patients with a complete and sustained response to immunotherapy (N = 15, male 80%, average age 61.0 ±12.2 years) were prospectively profiled for gut (faecal) microbiota signatures and dietary intake (four 24-hour recalls three weeks before the stool sample). Patients were grouped regarding the average DF intake of ≥ 25g/day (high fibre group HFG, N=8) and < 25g/day (low fibre group LFG, N=7).

Results: HFG had significantly higher intake and energy proportion of mono-unsaturated fatty acids (p=0.007) and omega-3 fatty acids (p=0.049), and lower alcohol intake (p=0.046) than LFG patients. HFG patients showed an increase in the proportion of Phocaeicola dorei, Bacteroides cellulosilyticus and Holdemania massiliensis on LEfSE analysis, while LFG exhibited a higher abundance of Ruminococcus, Blautia wexlerae, Anaerobytricum hellii, and Ruthenibacterium edouardi.

Conclusion: DF and omega-3 fatty acids have proven to be associated with promoting intestinal integrity, enhancing short-chain fatty acid production, and altering gut inflammatory state. We demonstrated differences in gut microbiome composition between HFG and LFG metastatic melanoma patients with complete and sustained response to immunotherapy; which further exhibits a potential for health and intestinal homeostasis. The presented difference could be explained by the causal variance in intestinal microbial community ecology that is possibly affected by various environmental involvements, such as diet.

Bifidobacterium animalis subsp. lactis (BAL) is a well-known probiotic. Laetiporus sulphureus is an edible mushroom with a recognizable effect on human health. A single and synergistic effect of BAL and BAL/ethyl acetate extract of L. sulphureus (EALS) on the levels of (superoxide anion radical) O₂^-. and (reduced glutathione) GSH in (healthy lung fibroblast) MRC-5 and (colorectal cancer cells - CRC) HCT-116 cells have been poorly explored. It is known that increased production of O₂^-. underlies carcinogenesis. GSH is crucial for the maintenance of redox balance in cells, and it is the first defense line from O₂^-.. Our study aimed to investigate the effect of BAL, and co-treatment BAL/EALS (concentrations 10 and 50 µg/mL) on O₂^-. and GSH levels in the MRC-5 and HCT-116 cells. Incubation of the MRC-5 and HCT-116 cells with the probiotics and EALS extract was performed in a simple co-culture system. The O₂^-. and GSH levels were measured spectrophotometrically after 12 and 24 h. The levels of O₂^-. and GSH were increased in the treated MRC-5 cells, especially after the BAL/EALS (50 µg/mL) co-treatment. In the treated HCT-116 cells, O₂^-. remained at a low level and GSH concentration decreased after 12 h. After 24 h of incubation, the BAL and BAL/EALS increased the level of GSH in the treated cells when compared with control (untreated) cells. High GSH levels after 12 h indicate that the MRC-5, as healthy cells, strongly reacted to changes in oxidative stress parameters. So, these cells were more sensitive to treatments when compared with the HCT-116 cells isolated from CRC. Lower O₂^-. and GSH values in the HCT-116 cells, especially at 12 h, show oxidative stress resistance which is one of the main characteristics of CRC cells. These results can be explained by the fact that MRC-5 cells do not physiologically interact with BAL, while HCT-116 cells are epithelial cells from CRC and these cells are familiar with the presence of BAL in human colon.

Background and aims

Obesity is a public health problem of high incidence worldwide. The usual treatment is a reduction in calorie intake and an increase in energy expenditure, but not all individuals respond equally to these treatments. Epigenetics could be a factor that contributes to this heterogeneity. The aim of this research was to determine the association between DNA methylation at baseline and the percentage of BMI loss after two dietary interventions, in order to design a prediction model to evaluate the percentage of BMI loss based on methylation data.

Methods and Results

Spanish participants with overweight or obesity (n=306) were randomly assigned to two lifestyle interventions with hypocaloric diets: one moderately high in protein (MHP) and the other low in fat (LF) during 4 months (Obekit study). DNA methylation was analyzed in white blood cells using the Infinium MethylationEPIC array.

After identifying those methylation sites SD>0.1 and associated with the percentage of BMI loss (p<0.19 in the multiple regression model), two weighted methylation subscores were constructed for each diet: 15 CpGs were used for MHP diet and 11 CpGs for LF diet. Afterwards, a total methylation score was made by subtracting the previous subscores. These data were used to design a prediction model for the percentage of BMI loss through a linear mixed effect model in which the interaction between diet and total score was analyzed.

Conclusion

Overall, DNA methylation predicts the percentage of BMI loss of two hypocaloric diets after 4 months and was able to determine which type of diet is the most appropriate for each individual. These results confirm that epigenetic biomarkers may be further used for precision nutrition and the design of personalized dietary strategies against obesity.