Untargeted metabolomics in gastric and colorectal cancer patients - preliminary results.

Introduction: Recent years, microbiota-associated aspects have been analysed in multiple disorders regarding cancers. Existing evidence pints that gut microorganisms might take part in tumour origin and therapy efficacy. Nevertheless, to date, data on faecal metabolomics in cancer patients is still strongly limited. Therefore, we aimed to analyse gut untargeted metabolome in gastrointestinal cancer patients (i.e., gastric and colorectal cancer). Patients and methods: There were 12 patients with either gastric (n=4) or colorectal cancer (n=8) enrolled and 8 analysed (n=4 each). Stool samples were collected prior to anti-cancer treatments. Untargeted metabolomics analyses were conducted by means of mass spectrometry. Results: A plethora of metabolites in cancer patients we analysed were noted, with higher homogenity in case of gastric cancer patients. We found that the level of Deoxyguanosine,m/z 266.091,[M-H]-, Uridine,m/z 245.075,[M+H]+, Deoxyguanosine,m/z 268.104,[M]+, 3-Indoleacetic acid,m/z 176.07,[M+H]+, Indoxyl,m/z 132.031,[M-H]-, L-Phenylalanine,m/z 164.073,[M-H]-, L-Methionine,m/z 150.058,[M+NH4]+, was significantly higher in colorectal cancer patients and Ethyl hydrogen malonate,m/z 133.031,[M+H]+ in gastric cancer. Conclusion: The overall insights into untargeted metabolomics showed that most often higher levels of analysed metabolites were detected in colorectal cancer patients compared to gastric cancer patients. The link between gut metabolome and both local and distal metastasis might exist, however it requires confirmation in further multi-centre studies regarding larger sample size.

Altered lipid metabolism in patients with acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.

Multispecies probiotic affects fecal short-chain fatty acids in postmenopausal women with obesity: A post hoc analysis of a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Probiotics are known to regulate host metabolism. The aim of this study was to assess whether interventions with a multi-strain probiotic formula affect fecal short-chain fatty acids (SCFAs). METHODS: The analysis was carried out in 56 obese, postmenopausal women randomized to three groups: probiotic dose 2.5 × 109 CFU/d (n = 18; lower probiotic dose [LPD]), 1 × 1010 CFU/d (n = 18; higher probiotic dose [HPD]), or placebo (n = 20). RESULTS: An increase in three SCFA fecal concentrations in the HPD group was observed: acetic acid (C2; effect [E] = 1.72, SE = 0.73; 95% confidence interval [CI], 0.28-3.16; P = 0.019), butyric acid (C4; E = 0.98, SE = 0.46; 95% CI, 0.08-1.88; P = 0.033), and valeric acid (C5; E = 0.68, SE = 0.23; 95% CI, 0.23-1.12; P = 0.003). The mediation analysis showed that the decrease in uric acid under HPD may be transmitted through the elevation of C5 content. Multi-strain probiotic increases the SCFA content in the stool in a dose-dependent manner, which may diminish some cardiovascular risk factors because of a reduction in blood uric acid levels. CONCLUSION: Assessing long-term health benefits requires further research, including assessment of blood SCFA concentrations and multiomic and mechanistic approaches.

Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study.

BACKGROUND: Microbiota and its metabolites are known to regulate host metabolism. In cross-sectional study conducted in postmenopausal women we aimed to assess whether the microbiota, its metabolites and gut barrier integrity marker are correlated with cardiometabolic risk factors and if microbiota is different between obese and non-obese subjects. METHODS: We analysed the faecal microbiota of 56 obese, postmenopausal women by means of 16S rRNA analysis. Stool short chain fatty acids, calprotectin and anthropometric, physiological and biochemical parameters were correlates to microbiome analyses. RESULTS: Alpha-diversity was inversely correlated with lipopolysaccharide (Rho = - 0.43, FDR P (Q) = 0.004). Bray-Curtis distance based RDA revealed that visceral fat and waist circumference had a significant impact on metabolic potential (P = 0.003). Plasma glucose was positively correlated with the Coriobacteriaceae (Rho = 0.48, Q = 0.004) and its higher taxonomic ranks, up to phylum (Actinobacteria, Rho = 0.46, Q = 0.004). At the metabolic level, the strongest correlation was observed for the visceral fat (Q < 0.15), especially with the DENOVOPURINE2-PWY, PWY-841 and PWY0-162 pathways. Bacterial abundance was correlated with SCFAs, thus some microbiota-glucose relationships may be mediated by propionate, as indicated by the significant average causal mediation effect (ACME): Lachnospiraceae (ACME 1.25, 95%CI (0.10, 2.97), Firmicutes (ACME 1.28, 95%CI (0.23, 3.83)) and Tenericutes (ACME - 0.39, 95%CI (- 0.87, - 0.03)). There were significant differences in the distribution of phyla between this study and Qiita database (P < 0.0001). CONCLUSIONS: Microbiota composition and metabolic potential are associated with some CMRF and fecal SCFAs concentration in obese postmenopausal women. There is no unequivocal relationship between fecal SCFAs and the marker of intestinal barrier integrity and CMRF. Further studies with appropriately matched control groups are warranted to look for causality between SCFAs and CMRF.

Rotating Magnetic Field Increases ß-Lactam Antibiotic Susceptibility of Methicillin-Resistant Staphylococcus aureus Strains.

Methicillin-resistant strains of Staphylococcus aureus (MRSA) have developed resistance to most ß-lactam antibiotics and have become a global health issue. In this work, we analyzed the impact of a rotating magnetic field (RMF) of well-defined and strictly controlled characteristics coupled with ß-lactam antibiotics against a total of 28 methicillin-resistant and sensitive S. aureus strains. The results indicate that the application of RMF combined with ß-lactam antibiotics correlated with favorable changes in growth inhibition zones or in minimal inhibitory concentrations of the antibiotics compared to controls unexposed to RMF. Fluorescence microscopy indicated a drop in the relative number of cells with intact cell walls after exposure to RMF. These findings were additionally supported by the use of SEM and TEM microscopy, which revealed morphological alterations of RMF-exposed cells manifested by change of shape, drop in cell wall density and cytoplasm condensation. The obtained results indicate that the originally limited impact of ß-lactam antibiotics in MRSA is boosted by the disturbances caused by RMF in the bacterial cell walls. Taking into account the high clinical need for new therapeutic options, effective against MRSA, the data presented in this study have high developmental potential and could serve as a basis for new treatment options for MRSA infections.

Potato Juice, a Starch Industry Waste, as a Cost-Effective Medium for the Biosynthesis of Bacterial Cellulose.

In this work, we verified the possibility of valorizing a major waste product of the potato starch industry, potato tuber juice (PJ). We obtained a cost-effective, ecological-friendly microbiological medium that yielded bacterial cellulose (BC) with properties equivalent to those from conventional commercial Hestrin-Schramm medium. The BC yield from the PJ medium (>4 g/L) was comparable, despite the lack of any pre-treatment. Likewise, the macro- and microstructure, physicochemical parameters, and chemical composition showed no significant differences between PJ and control BC. Importantly, the BC obtained from PJ was not cytotoxic against fibroblast cell line L929 in vitro and did not contain any hard-to-remove impurities. The PJ-BC soaked with antiseptic exerted a similar antimicrobial effect against Staphylococcus aureus and Pseudomonas aeruginosa as to BC obtained in the conventional medium and supplemented with antiseptic. These are very important aspects from an application standpoint, particularly in biomedicine. Therefore, we conclude that using PJ for BC biosynthesis is a path toward significant valorization of an environmentally problematic waste product of the starch industry, but also toward a significant drop in BC production costs, enabling wider application of this biopolymer in biomedicine.

The Effects of Immunosuppressive Treatment during Pregnancy on the Levels of Potassium, Iron, Chromium, Zinc, Aluminum, Sodium and Molybdenum in Hard Tissues of Female Rats and Their Offspring.

The ideal immunosuppressive regimen should provide for excellent immunosuppression with no side effects. Yet, current immunosuppressive therapy regimens commonly used in clinical applications fail to meet this criterion. One of the complications caused by immunosuppressive drugs is mineralization disorders in hard tissues. In this study, we evaluated the effects of three immunosuppressive therapies used after transplantation on the levels of potassium, iron, chromium, zinc, aluminum, sodium and molybdenum in the bones and teeth of female rats and their offspring. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The hard tissues of rats were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebulizer and a cyclonic spray chamber. All the immunosuppressive regimens included in the study affected the concentrations of the studied minerals in hard tissues of female rats and their offspring. The therapy based on cyclosporine A, everolimus and prednisone led to a decline in the levels of iron in bone, zinc in teeth, and molybdenum in the bone and teeth of mothers, while in the offspring, it caused a decline of bone potassium, with a decrease in iron and increase of molybdenum in teeth. Moreover, the regimen caused an increase in aluminum and chromium in the teeth and aluminum in the bones of the offspring, and consequently, it seems to be the therapy with the most negative impact on the mineral metabolism in hard tissues.

Can the FUT 2 Gene Variant Have an Effect on the Body Weight of Patients Undergoing Bariatric Surgery?-Preliminary, Exploratory Study.

BACKGROUND: The FUT2 gene (Se gene) encoding the enzyme α-1,2-L-fucosyltransferase 2 seems to have a significant effect on the number and type of bacteria colonizing the intestines. METHODS: In a group of 19 patients after bariatric surgery, the polymorphism (rs601338) of FUT2 gene was analyzed in combination with body mass reduction, intestinal microbiome (16S RNA sequencing), and short chain fatty acids (SCFA) measurements in stools. RESULTS: Among the secretors (Se/Se polymorphism of the FUT2 gene rs601338, carriers of GG variant), correlations between waist-hip ratio (WHR) and propionate content and an increase in Prevotella, Escherichia, Shigella, and Bacteroides were observed. On the other hand-in non-secretors (carriers of GA and AA variants)-higher abundance of Enterobacteriaceae, Ruminococcaceae, Enterobacteriaceae, Clostridiales was recorded. CONCLUSIONS: The increased concentrations of propionate observed among the GG variants of FUT 2 may be used as an additional source of energy for the patient and may have a higher risk of increasing the WHR than carriers of the other variants (GA and AA).

Effect of fluoride on endocrine tissues and their secretory functions -- review.

The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.

Bioelements in the treatment of burn injuries - The complex review of metabolism and supplementation (copper, selenium, zinc, iron, manganese, chromium and magnesium).

Appropriate nutrition is a key component of burn treatment and should be regarded as an integral part of the therapeutic process in burn patients. A nutritional intervention plan should not only allow for adequate quantities of energy and protein but also carefully consider the supply of macro- and micronutrients. As a result of the severe inflammatory response, oxidative stress, and hypermetabolic state, accompanied by often extensive exudation in burn patients, there is a considerable loss of macro- and micronutrients, including essential trace elements. This leads to certain complications, involving e.g. more frequent infections and impaired wound healing. Our current body of knowledge is still insufficient, and the studies carried out to date focus for the most part on the imbalances in trace elements, such as copper (Cu), selenium (Se), and zinc (Zn). Nevertheless, there are many other trace elements involved in immune functions, regulating gene expression or antioxidant defense, and many of those have not been properly investigated in a clinical setting. Due to the insufficient amount of unambiguous literature data and relatively few, often dated, studies carried out with small patient groups, further evaluation of macro- and microelements in burn patients seems indispensable, e.g. to bring up to date local nutritional protocols.

Chronic Exposure to Fluoride Affects GSH Level and NOX4 Expression in Rat Model of This Element of Neurotoxicity.

Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT-PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood-brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines.

Can Functional Beverages Serve as a Substantial Source of Macroelements and Microelements in Human Nutrition?-Analysis of Selected Minerals in Energy and Isotonic Drinks.

Studies on the ingredients of energy drinks and isotonic drinks focus mainly on the evaluation of their content in terms of substances modulating the body's metabolism or those regarded as food additives. Having regard to the widespread availability of these beverages, their diversity and the limited number of studies in this area, the aim of this study was to analyse the contents of F, Al, Cd, Cr, Mn, V, Co, Ni, Zn, Bi and Na in the energy drinks and isotonic drinks available in the Polish market. Fluorine concentration was analysed using an ion-selective electrode. The other elements were analysed using ICP-OES. Obtained results showed that functional beverages need to be taken into account as a source of macroelements and microelements in human nutrition, particularly when ingested often and in large quantities (which applies particularly to the young population). Moreover, due caution needs to be maintained in consumer choices.

The influence of polyphenols on metabolic disorders caused by compounds released from plastics - Review.

Persistent organic pollutants (POPs) released from plastics into water, soil and air are significant environmental and health problem. Continuous exposure of humans to these substances results not only from the slow biodegradation of plastics but also from their ubiquitous use as industrial materials and everyday products. Exposure to POPs may lead to neurodegenerative disorders, induce inflammation, hepatotoxicity, nephrotoxicity, insulin resistance, allergies, metabolic diseases, and carcinogenesis. This has spurred an increasing intense search for natural compounds with protective effects against the harmful components of plastics. In this paper, we discuss the current state of knowledge concerning the protective functions of polyphenols against the toxic effects of POPs: acrylonitrile, polychlorinated biphenyls, dioxins, phthalates and bisphenol A. We review in detail papers from the last two decades, analyzing POPs in terms of their sources of exposure and demonstrate how polyphenols may be used to counteract the harmful environmental effects of POPs. The protective effect of polyphenols results from their impact on the level and activity of the components of the antioxidant system, enzymes involved in the elimination of xenobiotics, and as a consequence - on the level of reactive oxygen species (ROS). Polyphenols present in daily diet may play a protective role against the harmful effects of POPs derived from plastics, and this interaction is related, among others, to the antioxidant properties of these compounds. To our knowledge, this is the first extensive review of in vitro and in vivo studies concerning the molecular mechanisms of interactions between selected environmental toxins and polyphenols.

Diet-Induced Rat Model of Gradual Development of Non-Alcoholic Fatty Liver Disease (NAFLD) with Lipopolysaccharides (LPS) Secretion.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized Western countries. The prevalence of the disease is estimated to range from 4% to 46% worldwide. The aim of study was to develop an animal model with gradual NAFLD development. METHODS: Sprague-Dawley rats were fed a high-fat and high-cholesterol (HFHCh) diet. The rats from the study and control groups were sacrificed after 2, 4, 8, 12, 16, and 20 weeks of dietary exposure. RESULTS: Analysis of biochemical parameters showed that after only two weeks, ALT and cholesterol concentration in serum were elevated. After 4 weeks, TNF-α and HOMA-IR were significantly higher compared to the control group. NAFLD progression started after 12 weeks of diet-weight gain and increased LPS secretions were noticed. During the experiment, rats induced steatosis (from stage 0/1 after 4 weeks to stage 2/3 after 20 weeks), inflammation (from stage 0/1 after 4 weeks to stage 1/2 after 20 weeks), and fibrosis (from stage 1 after 12 weeks to stage 2 after 20 weeks). CONCLUSION: We can assume that the presented model based on the HFHCh diet induced gradual development of NAFLD. We confirmed that the animal NAFLD model increases LPS secretions during disease progression.