Background Metformin is the cornerstone therapy for type 2 diabetes, but gastrointestinal intolerance commonly limits dose escalation and long-term adherence. In the ProGasMet trial, multi-strain probiotic supplementation improved metformin tolerability. However, the underlying microbiome-metabolome mechanisms remain unclear. Methods and analysis We performed an exploratory multi-omics analysis using Period 1 of a randomized, double-blind, placebo-controlled trial. Participants with metformin intolerance received a multi-strain probiotic or placebo for 12 weeks. Paired stool samples collected at baseline and end of treatment were available from 34 participants (68 samples). We integrated shotgun metagenomic species profiles, predicted gut metabolic modules, and untargeted faecal LC-MS metabolomics using multi-block sparse PLS (DIABLO), complemented by longitudinal covariate-adjusted feature-level analyses and associations with gastrointestinal symptom burden (QACSMI and a simplified GI score). Results In multi-omics integration at 12 weeks, bile acid-related metabolites were among the strongest contributors to group separation, with hyodeoxycholic acid and related compounds enriched in the probiotic arm. Global biodiversity and community-wide turnover did not differ between groups. Feature-level analyses suggested modest, directionally coherent changes in selected taxa, functional modules, and metabolites. Higher hyodeoxycholic acid concentrations were associated with lower gastrointestinal symptom burden in probiotic-treated participants, a pattern not observed under placebo. Conclusion Probiotic supplementation may be associated with coordinated microbiome-metabolome shifts in metformin-intolerant type 2 diabetes, highlighting bile acid remodelling, particularly hyodeoxycholic acid, as a plausible candidate for improved tolerability. These results support prioritising secondary bile acid-microbiome pathways for confirmation in larger trials incorporating targeted bile acid quantification and causal modelling.
Background: Irritable Bowel Syndrome (IBS) is a complex disorder characterized by altered gut–brain interactions, with gastrointestinal microbiota and metabolic dysregulation playing key roles in its pathophysiology. Identifying specific metabolic alterations within the colonic mucosa may enhance our understanding of IBS and contribute to improved diagnostic and therapeutic approaches. Methods: This cross-sectional study analyzed the metabolomic profiles of colonic mucosal biopsies from 44 IBS patients assessed with ROME IV criteria and 69 healthy controls undergoing colonoscopy. Untargeted metabolomic profiling was conducted using liquid chromatography–mass spectrometry (LC-MS), and differential metabolite analysis was performed via fold-change calculations and machine learning-based classification. Results: IBS patients exhibited distinct mucosal metabolic profiles, with significantly elevated levels of N-acetylneuraminic acid and 1-palmitoylglycerol, suggesting compromised epithelial integrity and increased gut permeability. In contrast, cis-4-hydroxycyclohexanecarboxylic acid, a metabolite associated with protective mucosal functions, was reduced. Random Forest analysis identified these metabolites as key discriminatory features between IBS and control groups, reinforcing their potential role as biomarkers for IBS-related mucosal alterations. Conclusions: Our study highlights the unique metabolomic signatures of IBS at the mucosal level, emphasizing the role of microbial metabolites in disease pathology. These findings may facilitate the development of novel diagnostic tools and targeted therapeutic strategies, advancing personalized management for IBS patients.
The urobiome, or urinary tract microbiome, has emerged as a crucial component in maintaining urinary health and defending against infections. Recent advances in next-generation sequencing (NGS) have debunked the long-held belief that the urinary tract is sterile, revealing a unique ecosystem of microorganisms. The urobiome interacts with the urothelium and mucosa-associated lymphoid tissue (MALT) to support local immunity, playing an integral role in defending the urinary tract against pathogens. Through complex communication processes like quorum sensing, the urobiome regulates microbial behavior and controls interactions with host tissues, helping to prevent pathogen colonization and infection. However, dysbiosis in the urobiome can disrupt this balance, making the urinary tract more susceptible to infections, including urinary tract infections (UTIs). Studies have highlighted specific microbial compositions associated with both healthy and disease states, suggesting that shifts in the urobiome may correlate with various urological diseases. Furthermore, microbial diversity within the urinary tract differs by factors such as age and gender, reflecting the dynamic nature of the urobiome. Future research focusing on the interplay between the urobiome, host immune defenses, and pathogenic mechanisms may lead to innovative diagnostic and therapeutic approaches. Understanding how microbial composition changes during disease states could enable targeted treatments, potentially reducing reliance on antibiotics and minimizing resistance issues. The urobiome thus represents a promising frontier in urology, with implications for enhancing urinary health and treating infections more effectively.
Background: The intestinal microflora is a population of microorganisms that resides in the human gastrointestinal tract and is important in maintaining metabolic and immune homeostasis in the body. Bacteria residing in the intestine produce short-chain fatty acids (SCFAs), which communicate with, among other things, the brain-gut axis-disorders of which are one of the causes of MS-like pathologies. A particular property of SCFAs is the induction of regulatory T cells, which are finding their way into pioneering therapies for MS patients. The aim of the study is to evaluate SCFA secretion in patients with multiple sclerosis from the West Pomeranian region depending on the genotypes of rs778986 and rs3894326 polymorphisms of the FUT3 gene. Methods: The study group included 47 patients clinically diagnosed with MS. Genotyping was performed by real-time PCR using TaqMan probes. Analysis of short-chain fatty acids in faeces was performed on a quadrupole mass spectrometer coupled to a time-of-flight (QTOF) analyser coupled to an AB Sciex high-performance liquid chromatograph (UHPLC). Results: Statistical analysis did not reveal any statistically significant differences in the prevalence of the studied polymorphisms in MS patients compared to the healthy control group. It was observed that the intestinal microflora and SCFA production in MS patients may be disturbed, while the studied FUT3 gene polymorphisms probably do not have a significant effect on their concentrations. A statistical tendency towards higher caproic acid content in heterozygotes of the rs778986 polymorphism and higher valeric acid secretion in homozygotes of rs3894326 was demonstrated. Conclusions: In summary, the studied FUT3 gene polymorphisms are not overrepresented in patients with MS. The rs778986 FUT3 polymorphism may affect the caproic acid content in the faeces of patients with MS, and the rs3894326 polymorphism may affect valeric acid secretion. Due to the small sample size and sparse genotype groups, the study has limited power and negative findings may reflect Type II error; replication in larger cohorts is warranted.
Background: Gut microbiota generates a series of bioactive metabolites that can be converted into uremic toxins such as trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), and indoxyl sulfate (IS). The aim of the study was to examine the association between diet and the concentrations of the mentioned gut microbiota-derived uremic toxins. Methods: An observational cross-sectional study was conducted involving 210 participants: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, 52 kidney transplant recipients (KTR), and 30 healthy controls. Dietary intake was assessed using a 3-day food diary and a food frequency questionnaire with 6 answers (FFQ-6). The alternate Mediterranean diet (aMED) score was calculated based on data obtained from the 3-day food diary and FFQ-6. Blood samples were analyzed for TMAO, pCS, and IS concentrations using liquid chromatography-mass spectrometry (LC-MS/MS). Results: Significant differences in TMAO, pCS, and IS concentrations were observed among the study groups. HD and PD patients exhibited higher levels of these metabolites compared to KTR and healthy controls. The median aMED score was 4 (3-5) points in the HD group, 4.5 (4-6) points in the PD group, 5 (4-6) points in the KTRs, and 6 (5-7) points in the control group. Higher adherence to the Mediterranean diet (aMED score) was associated with lower pCS levels in dialysis patients. Vegetable intake several times a day was found to mitigate the effects of phenylalanine and tyrosine intake on pCS concentration among dialysis patients. Conclusions: The diet of patients undergoing kidney replacement therapy (KRT) significantly affects the concentrations of gut microbiota-derived uremic toxins. These findings highlight the importance of dietary management in mitigating the adverse effects of these toxins in patients with chronic kidney disease (CKD). (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
OBJECTIVE:Accumulating preclinical and clinical evidence suggests potential beneficial effects of probiotic supplementation in the management of epilepsy. Here, we aimed to investigate the effect of two distinct bacterial strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility, the antiseizure efficacy of sodium valproate, behavioral and neurochemical parameters, and gut metabolomic profiles in mice. METHODS:Mice received daily oral administration of either B. longum R0175 or L. rhamnosus JB-1 for 28 d. Seizure thresholds were assessed using the maximal electroshock seizure threshold (MEST) test, the 6 Hz seizure threshold test, and the intravenous (iv) pentylenetetrazole (PTZ) seizure test. The efficacy of sodium valproate was evaluated in the subcutaneous (sc) PTZ seizure test. Additional assessments included anxiety-related behavior, neuromotor functions, brain neurochemical and inflammatory markers, fecal short-chain fatty acids (SCFAs), and untargeted metabolomic profiling of fecal samples. RESULTS:B. longum R0175 and L. rhamnosus JB-1 did not affect the thresholds for tonic seizures in the MEST test and for psychomotor seizures in the 6 Hz test. B. longum R0175 slightly increased the threshold for myoclonic seizures in the ivPTZ. Both strains enhanced the antiseizure efficacy of sodium valproate without altering its serum or brain concentrations. No significant effects were observed on anxiety-related behavior, neuromotor function, neurochemical or inflammatory markers. Both probiotics increased the concentration of butyrate and total SCFAs in fecal samples. Metabolomic analysis revealed variations in the metabolism of bile acids, polyphenols, fatty acids, and amino acids. CONCLUSIONS:The probiotics alone had minimal effects on seizure thresholds, but they enhanced the antiseizure efficacy of valproate, which may be linked to increased SCFA production and altered gut metabolism. These findings support further studies on probiotics as a complementary strategy in epilepsy treatment.
Dancers experience physical and psychological stressors that can impact gut health. We hypothesized that a three-month supplementation with Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 would result in measurable alterations in the fecal metabolomic profile and improve gastrointestinal symptomatology in dancers. Of the 51 volunteers, 26 female dancers were randomized to a 12-week trial (NCT05567653). A homogenous group of 16 (probiotic: n = 5; placebo: n = 11) was analyzed. The participants received L. helveticus R0052 and B. longum R0175 (3 × 109 colony-forming units/day) or a placebo. Baseline dietary intake and body composition were recorded. Fecal samples were analyzed using liquid chromatography-mass spectrometry, and gastrointestinal symptoms were assessed with the Rome IV questionnaire. Statistical methods included principal component analysis, mixed-effects models, and analysis of variance-simultaneous component analysis (ASCA). The study revealed shifts in the probiotic group's fecal metabolome (permutation test p = 0.026), including a reduction in (2RS)-2-(4-hydroxyphenyl)propionic acid (p = 0.023). No improvement in gastrointestinal symptoms was observed. No adverse events occurred. L. helveticus R0052 and B. longum R0175 may alter the gut metabolome, notably (2RS)-2-(4-hydroxyphenyl)propionic acid, but small sample size and absent symptom improvement limit the conclusions. Larger studies with varied doses and blood metabolite analysis are needed to confirm relevance.
IntroductionRecent 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 methodsThere 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.ResultsA 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.ConclusionThe 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.
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.
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 & POUND; 109 CFU/d (n = 18; lower probiotic dose [LPD]), 1 & POUND; 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. & COPY; 2023 Elsevier Inc. All rights reserved.
Abstract 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.
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.
Methicillin-resistant strains of Staphylococcus aureus (MRSA) have developed resistance to most beta-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 beta-lactam antibiotics against a total of 28 methicillin-resistant and sensitive S. aureus strains. The results indicate that the application of RMF combined with beta-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 beta-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.
Immunosuppressive therapy is necessary to prevent transplant rejection, also in the case of pregnant transplant recipients, which means that the medications may influence foetal development. An ideal immunosuppressive regimen should provide for excellent immunosuppression with minimal or 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 are mineralisation disorders in hard tissues. Therefore, in this study, we evaluated the impact of three regimens of immunosuppressive therapy used after renal transplantation, containing medications which are indicated (prednisone, cyclosporine A (CsA), tacrolimus (Tc)) and contraindicated (mycophenolate mofetil (MMF), everolimus) during pregnancy on the concentrations of essential minerals, calcium (Ca), phosphorus (P) and magnesium (Mg), affecting normal bone formation. The samples were analysed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebuliser and a cyclonic spray chamber. The immunosuppressive regimens under study had no effect on the levels of Mg and P, but they did contribute to increased bone Ca levels in the mothers in the group receiving Tc, MMF and prednisone and group receiving CsA, everolimus and prednisone. In the offspring of tested mother rats, immunosuppressive therapies may affect Mg levels in hard tissues. The immunosuppressive regimens administered at therapeutic doses are harmful to rat foetuses as evidenced by the small number or lack of offspring in the tested groups.
Methicillin-resistant strains of Staphylococcus aureus (MRSA) have developed resistance to most β-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 β-lactam antibiotics against a total of 28 methicillin-resistant and sensitive S. aureus strains. The results indicate that the application of RMF combined with β-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 β-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.
Goutweed (Aegopodium podagraria L.) is a common plant in the Apiaceae family. It occurs in Europe, North America and Asia. In folk medicine, mainly the leaves of goutweed were used to treat gout, inflammatory states in kidneys and bladder and to facilitate wound healing. Chemical composition of goutweed has not been entirely determined, however, it is known that the main group of compounds are polyacetylenes (falcarinol and falcarindiol). Moreover, other compounds were isolated from this plant, such as essential oils from the group of mono- and sesquiterpenes, as well as coumarins and polyphenol compounds, e.g. phenolic acids and flavonoids. Preparations from goutweed have anti-inflammatory and antimicrobial properties. Research performed in recent years have shown the possibilities to use tinctures and extracts from goutweed in the treatment of gout and metabolic diseases including type 2 diabetes.
The healing properties of hemp agrimony (Eupatorium cannabinum L.) have been already described in the seventeenth-century Polish medical herbaria. These historical descriptions also pointed to their potential anticancer activity. Contemporary literature data confirm the presence of many bioactive compounds in hemp agrimony, but there are few data confirming their anti-cancer properties. Phytotherapy is used as a form of natural treatment or supporting conventional methods of therapy of many diseases. Supplementation with herbal preparations is currently very popular, which is why it seems important to study the anti-cancer potential of these plants. Aqueous extract: 10 g of dried aerial part of plants was extracted in water at temp. 80*C for 3h and filtered, evaporated, and reconstituted in water to a final stock solution (100 mg/mL). Cytotoxicity assay: The effects of plant extracts on cell growth were determined by incubating cells with different concentrations for 72 h at 37°C in standard 96-well plates. The cell growth inhibition was determined by MTT reduction assay (spectrophotometric analysis). The aqueous extract showed a cytotoxic effect against U87 MG with IC50 values of 0,09±0,01 μg/mL. The plant revealed high total phenolic content, total flavonoid, and antioxidant capacity. The synergistic effect of bioactive compounds of hemp agrimony plausibly contributed to the cytotoxic effect of the extract. The presented results suggest that the historical description of the anti-cancer properties of hemp agrimony may have scientific justification and be the starting point for further research.
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).
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.
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.