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Analiza wolnego pozakomórkowego DNA o pochodzeniu bakteryjnym u pacjentów z zaawansowanym czerniakiem poddanych immunoterapii anty-PD-1
Influence of supplementation with iron and probiotic bacteria Lactobacillus plantarum and Lactobacillus curvatus on selected parameters of inflammatory state in rats on a high-fat iron-deficient diet
AbstractBACKGROUNDA high‐fat (HF) diet, diet iron deficiency and iron supplementation may affect inflammatory parameters. Probiotics influence both iron metabolism and inflammation. We compared the inflammatory state in rats on a HF iron‐deficient diet receiving oral iron, Lactobacillus plantarum and Lactobacillus curvatus in different combinations.METHODSThis was a two‐stage experiment. In groups C (n = 8) and HF (n = 8), rats ate a control or HF diet, respectively, for 16 weeks. In the group HFDEF (n = 48), rats ate a HF iron‐deficient diet for 8 weeks (first stage) and were subsequently divided into 6 groups (n = 8 each) receiving the following for a further 8 weeks (second stage): HFDEF – a HF iron‐deficient diet; HFDEFFe – a HF iron‐deficient diet with iron; HFDEFLp and HFDEFLc – a HF iron‐deficient diet with L. plantarum or L. curvatus, respectively; and HFDEFFeLp and HFDEFFeLc – a HF iron‐deficient diet with iron and L. plantarum or L. curvatus, respectively. Body composition analysis and blood sampling was performed. Markers of iron status and levels of total antioxidant status (TAS), C‐reactive protein (CRP), tumour necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) were measured in the blood.RESULTSTAS was higher in the HFDEF group (756.57 ± 489.53 ng mL−1) versus the HFDEFLc group (187.04 ± 47.84 ng mL−1; P = 0.022). No more differences were found between groups, or in TAS, CRP, TNF‐α and IL‐6 concentrations. Also, no differences were found between groups for alanine and aspartate aminotransferases, glucose, total cholesterol, low‐ and high‐density lipoproteins and triglycerides. TAS level was positively correlated with ferritin concentration, IL‐6 with TAS and TNF‐α with hepcidin level.CONCLUSIONSSupplementation with L. plantarum, L. curvatus and iron in combinations exerts no influence on inflammatory status, lipid profile, hepatic function and serum fasting glucose in rats on a HF iron‐deficient diet. © 2024 Society of Chemical Industry.
Influence of supplementation with probiotic bacteria Lactiplantibacillus plantarum and Latilactobacillus curvatus on selected parameters of duodenum iron metabolism in rats on a high-fat, iron-deficient diet
Circulating Cell-Free Microbial DNA Signatures and Plasma Soluble CD14 Level Are Associated with Clinical Outcomes of Anti-PD-1 Therapy in Advanced Melanoma Patients
An accumulating number of studies suggest the potential of circulating cell-free microbial DNA (cfmDNA) as a non-invasive biomarker in various diseases, including cancers. However, its value in the prediction or prognosis of clinical outcomes of immune checkpoint inhibitors (ICIs) is poorly explored. The circulating cfmDNA pool may also reflect the translocation of various microbial ligands to the circulatory system and may be associated with the increased release of soluble CD14 (sCD14) by myeloid cells. In the present study, blood samples were collected from advanced melanoma patients (n = 66) before and during the anti-PD-1 therapy (approximately 3 and 12 months after the start). Then, V3-V4 16S rRNA gene sequencing was performed to analyze the circulating cfmDNA extracted from plasma samples. Moreover, the concentration of plasma sCD14 was measured using ELISA. As a result, the differences in the circulating cfmDNA profiles were found between patients with favorable and unfavorable clinical outcomes of the anti-PD-1 and baseline signatures correlated with progression-free survival and overall survival. Moreover, there was a higher concentration of plasma sCD14 in patients with unfavorable clinical outcomes. High baseline sCD14 level and its increase during the therapy prognosticated worse survival outcomes. Taken together, this preliminary study indicates the potential of circulating cfmDNA signatures and plasma sCD14 levels as biomarkers of clinical outcomes of ICIs.
Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti–PD-1 Therapy
Abstract Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study, we found that melanoma patients exhibited a distinct gut mycobiota structure compared with healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, whereas Saccharomyces cerevisiae and Debaryomyces hansenii were less abundant. During anti–PD-1 treatment, the relative amount of Malassezia restricta and C. albicans increased. A higher level of Saccharomyces paradoxus was associated with a positive response to anti–PD-1 treatment, whereas a higher level of Tetrapisispora blattae was associated with a lack of clinical benefits. High levels of M. restricta and C. albicans, elevated serum lactate dehydrogenase, and being overweight were linked to increased risk of melanoma progression and poorer response to anti–PD-1 treatment. Thus, this study has revealed melanoma-associated mycobiome dysbiosis, characterized by altered fungal composition and fungi species associated with a higher risk of melanoma progression, identifying a role for the gut mycobiome in melanoma progression.
Impact of Lactobacillus acidophilus and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model
Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.
Charakterystyka frakcji mikrobioty jelitowej związanej z wydzielniczymi immunoglobulinami A (SlgA) u pacjentów z zaawansowanym czerniakiem poddanych immunoterapii anty-PD-1
Exploring correlations between gut mycobiome and lymphocytes in melanoma patients undergoing anti-PD-1 therapy
Abstract Research has shown that the microbiome can influence how the immune system responds to melanoma cells, affecting the course of the disease and the outcome of the therapy. Here, we used the metagenomic approach and flow cytometry analyses of blood cells to discover correlations between gut fungi of metastatic melanoma patients enrolled in anti-PD-1 therapy and lymphocytes in their blood. We analyzed the patterns of associations before the first administration of anti-PD-1 therapy (BT, n = 61) and in the third month of the therapy (T3, n = 37), allowing us to track changes during treatment. To understand the possible impact of gut fungi on the efficacy of anti-PD-1 therapy, we analyzed the associations in clinical beneficiaries (CB, n = 37) and non-beneficiaries (NB, n = 24), as well as responders (R, n = 28) and non-responders (NR, n = 33). Patients with LDH < 338 units/L, overall survival (OS) > 12, CB, as well as R, had lower levels of Shannon diversity (p = 0.02, p = 0.05, p = 0.05, and p = 0.03, respectively). We found that the correlation pattern between intestinal fungi and lymphocytes was specific to the type of response, positive or negative. When comparing CB and NB groups, correlations with opposite directions were detected for C. albicans, suggesting a response-specific immune reaction. For CB, M. restricta exhibited a set of correlations with different types of lymphocytes, with prevalent positive correlations, suggesting a robust immune response in the CB group. This result extends our former research, where M. restricta and C. albicans were associated with an increased risk of melanoma progression and a poorer response to anti-PD-1 treatment.