PubMed

Ecotoxicol Environ Saf. 2024 Jan 2;270:115922. doi: 10.1016/j.ecoenv.2023.115922. Online ahead of print.ABSTRACTBisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.PMID:38171106 | DOI:10.1016/j.ecoenv.2023.115922

Ecotoxicol Environ Saf. 2024 Jan 2;270:115898. doi: 10.1016/j.ecoenv.2023.115898. Online ahead of print.ABSTRACTCranial radiotherapy is an important treatment for intracranial and head and neck tumors. To investigate the effects of cranial irradiation (C-irradiation) on gut microbiota and metabolomic profile, the feces, plasma and cerebral cortex were isolated after exposing mice to cranial X-ray irradiation at a dose rate of 2.33 Gy/min (5 Gy/d for 4 d consecutively). The gut microorganisms and metabolites were detected by 16 S rRNA gene sequencing method and LC-MS method, respectively. We found that compared with sham group, the gut microbiota composition changed at 2 W and 4 W after C-irradiation at the genus level. The fecal metabolomics showed that compared with Sham group, 44 and 66 differential metabolites were found to be annotated into metabolism pathways at 2 W and 4 W after C-irradiation, which were significantly enriched in the arginine and proline metabolism. Metabolome analysis of serum and cerebral cortex showed that, at 4 W after C-irradiation, the expression pattern of metabolites in serum samples of mice was similar to that of sham group, and the cerebral cortex metabolites of the two groups were completely separated. KEGG functional analysis showed that serum and brain tissue differential metabolites were respectively enriched in tryptophan metabolism, and arginine proline metabolism. The correlation analysis showed that the changes of gut microbiota genera were significantly correlated with the changes of metabolism, especially Helicobacter, which was significantly correlated with many different metabolites at 4 W after C-irradiation. These data suggested that C-irradiation could affect the gut microbiota and metabolism profile, even at relatively long times after C-irradiation.PMID:38171101 | DOI:10.1016/j.ecoenv.2023.115898

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Dec 29;49:101175. doi: 10.1016/j.cbd.2023.101175. Online ahead of print.ABSTRACTDue to the strong response to air exposure, high mortality was occurred in Coilia nasus. Previous studies reported that 10 ‰ NaCl could significantly reduce mortality in C. nasus under air exposure. To investigate the mechanisms that 10 ‰ NaCl can alleviate stress, community structure and metabolism of the intestinal flora of C. nasus were detected via metagenome and metabolome. In this study, C. nasus were divided into control group (C), air exposure group without 10 ‰ NaCl (AE), and air exposure group with 10 ‰ NaCl (AES). After air exposure stress and salinity mitigation, the mortality, intestinal microorganisms, metabolites, and physiological biomarkers were analyzed. The results showed that the mortality rate of C. nasus was reduced after salinity reduction; the antioxidant capacity was elevated compared to the AE group; and anti-inflammatory capacity was increased in the AES group compared to the AE group. Metagenomic sequencing results showed that the levels of harmful bacteria (E. coli, Aeromonas) in the Candida nasus gut increased after air exposure; beneficial bacteria (Actinobacteria, Corynebacteria) in the C. nasus gut increased after salinity reduction. Metabolomics analyses showed that AE decreased the expression of beneficial metabolites and increased the expression of harmful metabolites; AES increased beneficial metabolites and decreased harmful metabolites. Correlation analysis showed that in the AE group, beneficial metabolites were negatively correlated with oxidative stress and inflammatory response, while harmful metabolites were positively correlated with oxidative stress and inflammatory response, and were associated with bacterial communities such as Gillisia, Alkalitalia, Avipoxvirus, etc.; the correlation of metabolites with oxidative stress and inflammatory response was opposite to that of AE in the case of AES, and was associated with Lentilactobacillus, Cyanobacterium, and other bacterial communities. Air exposure caused damage to Candida rhinoceros and 10 ‰ salinity was beneficial in alleviating C. nasus stress. These results will provide new insights into methods and mechanisms to mitigate stress in fish.PMID:38171069 | DOI:10.1016/j.cbd.2023.101175

Microbiol Spectr. 2024 Jan 3:e0203723. doi: 10.1128/spectrum.02037-23. Online ahead of print.ABSTRACTOur data revealed dynamic changes in vaginal, but not salivary, microbiome composition during the reproductive cycle of wild mice. With multiple OMICs platforms, we provide evidence that changes in microbiota in the vaginal environment are accompanied by changes in the proteomic and metabolomics profiles of the host. This study describes the natural microbiota of wild mice and may contribute to a better understanding of microbiome-host immune system interactions during the hormonal and cellular changes in the female reproductive tract. Moreover, analysis of volatiles in the vaginal fluid shows particular substances that can be involved in chemical communication and reproductive behavior.PMID:38171017 | DOI:10.1128/spectrum.02037-23

Sci Transl Med. 2024 Jan 3;16(728):eadg7740. doi: 10.1126/scitranslmed.adg7740. Epub 2024 Jan 3.ABSTRACTTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis. TNBCs with high homologous recombination deficiency (HRD) scores benefit from DNA-damaging agents, including platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, whereas those with low HRD scores still lack therapeutic options. Therefore, we sought to exploit metabolic alterations to induce HRD and sensitize DNA-damaging agents in TNBCs with low HRD scores. We systematically analyzed TNBC metabolomics and identified a metabolite, guanosine diphosphate (GDP)-mannose (GDP-M), that impeded homologous recombination repair (HRR). Mechanistically, the low expression of the upstream enzyme GDP-mannose-pyrophosphorylase-A (GMPPA) led to the endogenous up-regulation of GDP-M in TNBC. The accumulation of GDP-M in tumor cells further reduced the interaction between breast cancer susceptibility gene 2 (BRCA2) and ubiquitin-specific peptidase 21 (USP21), which promoted the ubiquitin-mediated degradation of BRCA2 to inhibit HRR. Therapeutically, we illustrated that the supplementation of GDP-M sensitized DNA-damaging agents to impair tumor growth in both in vitro (cancer cell line and patient-derived organoid) and in vivo (xenograft in immunodeficient mouse) models. Moreover, the combination of GDP-M with DNA-damaging agents activated STING-dependent antitumor immunity in immunocompetent syngeneic mouse models. Therefore, GDP-M supplementation combined with PARP inhibition augmented the efficacy of anti-PD-1 antibodies. Together, these findings suggest that GDP-M is a crucial HRD-related metabolite and propose a promising therapeutic strategy for TNBCs with low HRD scores using the combination of GDP-M, PARP inhibitors, and anti-PD-1 immunotherapy.PMID:38170790 | DOI:10.1126/scitranslmed.adg7740

Proc Natl Acad Sci U S A. 2024 Jan 9;121(2):e2316540120. doi: 10.1073/pnas.2316540120. Epub 2024 Jan 3.ABSTRACTHow the microaerobic pathogen Campylobacter jejuni establishes its niche and expands in the gut lumen during infection is poorly understood. Using 6-wk-old ferrets as a natural disease model, we examined this aspect of C. jejuni pathogenicity. Unlike mice, which require significant genetic or physiological manipulation to become colonized with C. jejuni, ferrets are readily infected without the need to disarm the immune system or alter the gut microbiota. Disease after C. jejuni infection in ferrets reflects closely how human C. jejuni infection proceeds. Rapid growth of C. jejuni and associated intestinal inflammation was observed within 2 to 3 d of infection. We observed pathophysiological changes that were noted by cryptic hyperplasia through the induction of tissue repair systems, accumulation of undifferentiated amplifying cells on the colon surface, and instability of HIF-1α in colonocytes, which indicated increased epithelial oxygenation. Metabolomic analysis demonstrated that lactate levels in colon content were elevated in infected animals. A C. jejuni mutant lacking lctP, which encodes an L-lactate transporter, was significantly decreased for colonization during infection. Lactate also influences adhesion and invasion by C. jejuni to a colon carcinoma cell line (HCT116). The oxygenation required for expression of lactate transporter (lctP) led to identification of a putative thiol-based redox switch regulator (LctR) that may repress lctP transcription under anaerobic conditions. Our work provides better insights into the pathogenicity of C. jejuni.PMID:38170751 | DOI:10.1073/pnas.2316540120

Neuropsychopharmacol Hung. 2023 Dec;25(4):183-193.ABSTRACTDepression is a highly prevalent and debilitating condition, yet we still lack both in-depth knowledge concerning its etiopathology and sufficiently efficacious treatment options. With approximately one third of patients resistant to currently available antidepressants there is a pressing need for a better understanding of depression, identifying subgroups within the highly heterogeneous illness category and to understand the divergent underlying biology of such subtypes, to help develop and personalise treatments. The TRAJECTOME project aims to address such challenges by (1) identifying depression-related multimorbidity subgroups and shared molecular pathways based on temporal disease profiles from healthcare systems and biobank data using machine learning approaches, and by (2) characterising these subgroups from multiple aspects including genetic variants, metabolic processes, lifestyle and environmental factors. Following the identification of multimorbidity trajectories, a disease burden score related to depression and adjusted for multimorbidity was established summarising the current state of the patient to weigh the molecular mechanisms associated with depression. In addition, the role of genetic and environmental factors, and also their interactions were identified for all subgroups. The project also attempted to identify potential metabolomic markers for the early diagnostics of these multimorbidity conditions. Finally, we prioritized molecular drug candidates matching the multimorbidity pathways indicated for the individual subgroups which would potentially offer personalised treatment simultaneously for the observable multimorbid conditions yet minimising polypharmacy and related side effects. The present paper overviews the TRAJECTOME project including its aims, tasks, procedures and accomplishments. (Neuropsychopharmacol Hung 2023; 25(4): 183-193)PMID:38170729

Curr Opin Clin Nutr Metab Care. 2023 Dec 26. doi: 10.1097/MCO.0000000000001007. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Most omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation clinical trials report inconsistent or null findings on measures of cognition or Alzheimer's disease (AD) with a relatively large variability in the response to n-3 PUFA supplementation. The purpose of this review is to identify whether the gut microbiome together with the metabolome can provide critical insights to understand this heterogeneity in the response to n-3 PUFA supplementation.RECENT FINDINGS: A Western diet with high saturated fat and omega-6 fatty acid content, obesity, and lack of exercise puts strain on the gut microbiome resulting in imbalance, dysbiosis, reduced bacterial diversity, and increased abundance of the pro-inflammatory taxa. A plant-based diet has beneficial effects on the gut microbiota even when deficient in n-3 PUFAs. Human and animal studies show that increased intake of the n-3 PUFAs correlates with increased beneficial intestinal bacteria when compared to a Western diet.SUMMARY: The composition of the gut microbiota can help define the effects of n-3 PUFA supplementation on the brain and lead to more personalized nutritional interventions.PMID:38170690 | DOI:10.1097/MCO.0000000000001007

STAR Protoc. 2024 Jan 1;5(1):102808. doi: 10.1016/j.xpro.2023.102808. Online ahead of print.ABSTRACTHere, we present a protocol for using Early Data Visualization Script, a user-friendly software tool to visualize complex volatile metabolomics data in clinical setups. We describe steps for tabulating data and adjusting visual output to visualize complex time-resolved volatile omics data using simple charts and graphs. We then demonstrate possible modifications by detailing procedures for the adaptation of four basic functions. For complete details on the use and execution of this protocol, please refer to Sukul et al. (2022)1 and Remy et al. (2022).2.PMID:38170664 | DOI:10.1016/j.xpro.2023.102808

Stem Cell Rev Rep. 2024 Jan 3. doi: 10.1007/s12015-023-10672-5. Online ahead of print.ABSTRACTAcute liver failure (ALF) results from severe liver damage or end-stage liver disease. It is extremely fatal and causes serious health and economic burdens worldwide. Once ALF occurs, liver transplantation (LT) is the only definitive and recommended treatment; however, LT is limited by the scarcity of liver grafts. Consequently, the clinical use of bioartificial liver (BAL) has been proposed as a treatment strategy for ALF. Human primary hepatocytes are an ideal cell source for these methods. However, their high demand and superior viability prevent their widespread use. Hence, finding alternatives that meet the seed cell quality and quantity requirements is imperative. Stem cells with self-renewing, immunogenic, and differentiative capacities are potential cell sources. MSCs and its secretomes encompass a spectrum of beneficial properties, such as anti-inflammatory, immunomodulatory, anti-ROS (reactive oxygen species), anti-apoptotic, pro-metabolomic, anti-fibrogenesis, and pro-regenerative attributes. This review focused on the recent status and future directions of stem cell-based strategies in BAL for ALF. Additionally, we discussed the opportunities and challenges associated with promoting such strategies for clinical applications.PMID:38170319 | DOI:10.1007/s12015-023-10672-5

Appl Microbiol Biotechnol. 2024 Dec;108(1):1-15. doi: 10.1007/s00253-023-12891-9. Epub 2024 Jan 3.ABSTRACTFungal infection has become a major threat to crop loss and affects food safety. The waste water from agar processing industries extraction has a number of active substances, which could be further transformed by microorganisms to synthesize antifungal active substances. In this study, Bacillus subtilis was used to ferment the waste water from agar processing industries extraction to analyze the antifungal activity of the fermentation broth on Alternaria alternata and Alternaria spp. Results showed that 25% of the fermentation broth was the most effective in inhibited A. alternata and Alternaria spp., with fungal inhibition rates of 99.9% and 96.1%, respectively, and a minimum inhibitory concentration (MIC) was 0.156 μg/mL. Metabolomic analysis showed that flavonoid polyphenols such as coniferyl aldehyde, glycycoumarin, glycitin, and procyanidin A1 may enhance the inhibitory activity against the two pathogenic fungal strains. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that polyphenols involved in the biosynthesis pathways of isoflavonoid and phenylpropanoid were upregulated after fermentation. The laser confocal microscopy analyses and cell conductivity showed that the cytoplasm of fungi treated with fermentation broth was destroyed. This study provides a research basis for the development of new natural antifungal agents and rational use of seaweed agar waste. KEY POINTS: • Bacillus subtilis fermented waste water has antifungal activity • Bacillus subtilis could transform active substances in waste water • Waste water is a potential raw material for producing antifungal agents.PMID:38170310 | DOI:10.1007/s00253-023-12891-9

Nutr Neurosci. 2024 Jan 3:1-14. doi: 10.1080/1028415X.2023.2301165. Online ahead of print.ABSTRACTOver recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the 'microbiota-gut-brain axis', the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.PMID:38170169 | DOI:10.1080/1028415X.2023.2301165

Front Oncol. 2023 Dec 19;13:1292046. doi: 10.3389/fonc.2023.1292046. eCollection 2023.ABSTRACTBreast cancer is the most common malignant neoplasm in women. Despite progress to date, 700,000 women worldwide died of this disease in 2020. Apparently, the prognostic markers currently used in the clinic are not sufficient to determine the most appropriate treatment. For this reason, great efforts have been made in recent years to identify new molecular biomarkers that will allow more precise and personalized therapeutic decisions in both primary and recurrent breast cancers. These molecular biomarkers include genetic and post-transcriptional alterations, changes in protein expression, as well as metabolic, immunological or microbial changes identified by multiple omics technologies (e.g., genomics, epigenomics, transcriptomics, proteomics, glycomics, metabolomics, lipidomics, immunomics and microbiomics). This review summarizes studies based on omics analysis that have identified new biomarkers for diagnosis, patient stratification, differentiation between stages of tumor development (initiation, progression, and metastasis/recurrence), and their relevance for treatment selection. Furthermore, this review highlights the importance of clinical trials based on multiomics studies and the need to advance in this direction in order to establish personalized therapies and prolong disease-free survival of these patients in the future.PMID:38169859 | PMC:PMC10758476 | DOI:10.3389/fonc.2023.1292046

Front Physiol. 2023 Dec 19;14:1306178. doi: 10.3389/fphys.2023.1306178. eCollection 2023.ABSTRACTBackground: Preclinical animal studies and clinical studies indicate that both maternal as well as paternal genetic alterations/gene defects might affect the phenotype of the next-generation without transmissions of the affected gene. Currently, the question of whether the same genetic defect present in the mother or father leads to a similar phenotype in the offspring remains insufficiently elucidated. Methods: In this head-to-head study, we crossbred female and male mice with heterozygous endothelial eNOS knockout (eNOS+/-) with male and female wild-type (wt) mice, respectively. Subsequently, we compared the phenotype of the resulting wt offspring with that of wt offspring born to parents with no eNOS deficiency. Results: Wt female offspring of mothers with heterozygous eNOS showed elevated liver fat accumulation, while wt male offspring of fathers with heterozygous eNOS exhibited increased fasting insulin, heightened insulin levels after a glucose load, and elevated liver glycogen content. By quantitative mass-spectrometry it was shown that concentrations of six serum metabolites (lysoPhosphatidylcholine acyl C20:3, phosphatidylcholine diacyl C36:2, phosphatidylcholine diacyl C38:1, phosphatidylcholine acyl-alkyl C34:1, phosphatidylcholine acyl-alkyl C36:3, and phosphatidylcholine acyl-alkyl C42:5 (PC ae C42:5) as well as four liver carbon metabolites (fructose 6-phosphate, fructose 1,6-bisphosphate, glucose 6-phosphate and fumarate) were different between wt offspring with eNOS+/- mothers and wt offspring with eNOS+/- fathers. Importantly, fumarate was inversely correlated with the liver fat accumulation in female offspring with eNOS+/- mothers and increased liver glycogen in offspring of both sexes with eNOS+/- fathers. The qRT-PCR results revealed that the gene expression patterns were different between wt offspring with eNOS+/- mothers and those offspring with eNOS+/- fathers. Different gene expression patterns were correlated with different observed phenotypic changes in male/female offspring born to mothers or fathers with a heterozygous eNOS genotype. Conclusion: The identical parental genetic alteration (heterozygous eNOS deficiency), without being passed on to the offspring, results in distinct metabolic, liver phenotype, and gene expression pattern variations depending on whether the genetic alteration originated from the father or the mother.PMID:38169827 | PMC:PMC10758467 | DOI:10.3389/fphys.2023.1306178

Biomed Rep. 2023 Dec 20;20(2):25. doi: 10.3892/br.2023.1713. eCollection 2024 Feb.ABSTRACTMicrobial metabolites play an important role in regulating intestinal homeostasis and immune responses. Propofol is a common anesthetic in clinic, but it is not clear whether it affects intestinal metabolites in rats. Tail vein puncture was performed after adaptive feeding for 1 month in eight 2-month-old rats and they were given continuous intravenous infusion of propofol for 3 h. The feces of rats were divided into different groups based on time periods, with before and after anesthesia with propofol on days 1, 3 and 7 labeled as groups P, A1, A3 and A7, respectively. The effect of continuous intravenous infusion with propofol on rat fecal metabolites was determined using the non-targeted metabolomics technique gas chromatography coupled with a time-of-flight mass spectrometer analysis. The types and contents of metabolites in rat feces were changed after continuous intravenous infusion with propofol, but the changes were not statistically significant. The contents of the metabolites 3-hydroxyphenylacetic acid and palmitic acid increased from day 3 to 7, and it was shown that the two metabolites were positively correlated at a statistically significant level. Linoleic acid decreased to its lowest level on day 3, and it returned to pre-anesthesia level on day 7. At the same time, linoleic acid metabolism was a metabolic pathway that was co-enriched 7 days after infusion with propofol. Spearman correlation analysis showed that there was significant correlation between some differential metabolites and differential microorganisms. It was observed that zymosterol 1, cytosin and elaidic acid were negatively correlated with Alloprevotella in the A3 vs. P group. In the A7 vs. P group, cortexolone 3 and coprostan-3-one were positively correlated with Faecalibacterium, whilst aconitic acid was negatively correlated with it. In conclusion, the present study revealed statistically insignificant effects of continuous intravenous propofol on the intestinal metabolites in rats.PMID:38169795 | PMC:PMC10758916 | DOI:10.3892/br.2023.1713

Heliyon. 2023 Dec 9;10(1):e23509. doi: 10.1016/j.heliyon.2023.e23509. eCollection 2024 Jan 15.ABSTRACTDespite advances in medical technology, lung cancer still has one of the highest mortality rates among all malignancies. Therefore, efforts must be made to understand the precise mechanisms underlying lung cancer development. In this study, we conducted lung and gut microbiome analyses and a comprehensive lipid metabolome analysis of host tissues to assess their correlation. Alternations in the lung microbiome due to lung cancer, such as a significantly decreased abundance of Firmicutes and Deferribacterota, were observed compared to a mock group. However, mice with lung cancer had significantly lower relative abundances of Actinobacteria and Proteobacteria and higher relative abundances of Cyanobacteria and Patescibacteria in the gut microbiome. The activations of retinol, fatty acid metabolism, and linoleic acid metabolism metabolic pathways in the lung and gut microbiomes was inversely correlated. Additionally, changes occurred in lipid metabolites not only in the lungs but also in the blood, small intestine, and colon. Compared to the mock group, mice with lung cancer showed that the levels of adrenic, palmitic, stearic, and oleic (a ω-9 polyunsaturated fatty acid) acids increased in the lungs. Conversely, these metabolites consistently decreased in the blood (serum) and colon. Leukotriene B4 and prostaglandin E2 exacerbate lung cancer, and were upregulated in the lungs of the mice with lung cancer. However, isohumulone, a peroxisome proliferator-activated receptor gamma activator, and resolvin (an ω-3 polyunsaturated fatty acid) both have anti-cancer effects, and were upregulated in the small intestine and colon. Our multi-omics data revealed that shifts in the microbiome and metabolome occur during the development of lung cancer and are of possible clinical importance. These results reveal one of the gut-lung axis mechanisms related to lung cancer and provide insights into potential new targets for lung cancer treatment and prophylaxis.PMID:38169741 | PMC:PMC10758782 | DOI:10.1016/j.heliyon.2023.e23509

Int J Med Sci. 2024 Jan 1;21(2):234-252. doi: 10.7150/ijms.85704. eCollection 2024.ABSTRACTLung cancer is a highly fatal disease that poses a significant global health burden. The absence of characteristic clinical symptoms frequently results in the diagnosis of most patients at advanced stages of lung cancer. Although low-dose computed tomography (LDCT) screening has become increasingly prevalent in clinical practice, its high rate of false positives continues to present a significant challenge. In addition to LDCT screening, tumor biomarker detection represents a critical approach for early diagnosis of lung cancer; unfortunately, no tumor marker with optimal sensitivity and specificity is currently available. Metabolomics has recently emerged as a promising field for developing novel tumor biomarkers. In this paper, we introduce metabolic pathways, instrument platforms, and a wide variety of sample types for lung cancer metabolomics. Specifically, we explore the strengths, limitations, and distinguishing features of various sample types employed in lung cancer metabolomics research. Additionally, we present the latest advances in lung cancer metabolomics research that utilize diverse sample types. We summarize and enumerate research studies that have investigated lung cancer metabolomics using different metabolomic sample types. Finally, we provide a perspective on the future of metabolomics research in lung cancer. Our discussion of the potential of metabolomics in developing new tumor biomarkers may inspire further study and innovation in this dynamic field.PMID:38169594 | PMC:PMC10758149 | DOI:10.7150/ijms.85704

Int J Med Sci. 2024 Jan 1;21(2):413-423. doi: 10.7150/ijms.89141. eCollection 2024.ABSTRACTIntroduction: Hepatocellular carcinoma (HCC) is the fourth most prevalent cancer in China. Transcatheter arterial chemoembolization (TACE) is a common interventional therapy for HCC. In this study, we aimed to explore specific metabolites that can accurately predict prognosis after TACE in patients with HCC. Methods: Patients with HCC and healthy volunteers (n = 20 each) were recruited to our study; plasma samples were collected from patients before and after TACE and from healthy volunteers. Plasma samples were subjected to untargeted ultra-high performance liquid chromatography-high resolution mass spectrometry metabolomics analysis, to identify metabolites significantly associated with the prognosis of patients with HCC after TACE. Results: Orthogonal filtered partial least squares discriminant analysis confirmed significant separation of the pre-TACE, post-TACE, and healthy groups, and 34 differential metabolites were identified between the pre-TACE and post-TACE groups. KEGG analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis pathways and the phenylalanine metabolism pathway were potentially altered in HCC genesis and during TACE. Phenylalanine and tyrosine are involved in both pathways and were increased in the pre-TACE group relative to controls, with phenylalanine further increased in the post-TACE group. Receiver operating characteristic (ROC) curve analysis indicated that PC 36:4|PC 18:2_18:2 (area under the ROC curve (AUC) = 0.798) is a potential marker for assessment of prognosis in patients with HCC after TACE. Moreover, ROC curve analysis indicated that palmitoylcarnitine (AUC = 1) is a marker with potential value for HCC diagnosis. Conclusions: Limited studies had been conducted on the detection of metabolites in the plasma of HCC patients before and after TACE. PC 36:4|PC 18:2_18:2 is a potential marker for evaluation of the therapeutic effects of TACE. This finding may be beneficial for the treatment of patients with HCC after TACE.PMID:38169572 | PMC:PMC10758137 | DOI:10.7150/ijms.89141

Biol Reprod. 2024 Jan 3:ioad175. doi: 10.1093/biolre/ioad175. Online ahead of print.ABSTRACTThe Yangtze finless porpoises (YFP; Neophocaena asiaeorientalis a.) is an endemic and critically endangered species in China. Intensive captive breeding is essential for understanding the biology of critically endangered species, especially their pregnancy characteristics, knowledge of which is crucial for effective breeding management. Urine metabolomics can reveal metabolic differences, arising from physiological changes across pregnancy stages. Therefore, we used the urinary metabolomic technology, to explore urinary metabolite changes in pregnant YFPs. A total of 2281 metabolites were identified in all samples, which including organic acids and derivatives (24.45%), organoheterocyclic compounds (20.23%), benzenoids (18.05%), organic oxygen compounds (7.73%) and phenylpropanoids and polyketides (6.48%). There were 164, 387, and 522 metabolites demonstrating differential abundance during early pregnancy (EP), mid pregnancy (MP), and late pregnancy (LP), respectively, from the levels observed in nonpregnancy. The levels of pregnenolone (P5), 17α-hydroxyprogesterone (17-HOP), and tetrahydrocortisone (THE) were significantly higher during all pregnancy stages, indicating their important roles in fetal development. The differential metabolites between nonpregnancy and pregnancy were mainly associated with amino acid and carbohydrate metabolism. Moreover, metabolic activity varied across pregnancy stages; steroid hormone biosynthesis was predominant in EP, and amino acid biosynthesis and carbohydrate metabolism were predominant in MP and LP, respectively. Our results provide new insights into metabolic characteristics in the YFPs urine during pregnancy, and indicate that the differential levels of urine metabolites can determine pregnancy in YFPs, providing valuable information for the husbandry and management of pregnant YFPs in captivity.PMID:38169437 | DOI:10.1093/biolre/ioad175

J Orthop Surg Res. 2024 Jan 3;19(1):6. doi: 10.1186/s13018-023-04486-x.ABSTRACTPURPOSE: Lower back pain (LBP), mainly caused by intervertebral disk (IVD) degeneration (IDD), is widely prevalent worldwide and is a serious socioeconomic burden. Numerous factors may trigger this degenerative process, and microbial dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between IDD and the microbiome remains obscure. In this study, we investigated the gut microbiota composition and fecal metabolic phenotype and discussed the possible influences of microbiome dysbiosis on IDD.METHODS: Fecal DNA was extracted from 16 fecal samples (eight rabbit models with IDD and eight sex- and age-matched healthy controls) and analyzed by high-throughput 16S rDNA sequencing. The fecal samples were also analyzed by liquid chromatography-mass spectrometry-based metabolomics. Multivariate analyses were conducted for the relationship between the omics data and IDD, linear discriminant analysis effect size was employed for biomarker discovery. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the differential metabolites. The potential correlation between differential gut microbiota and metabolites was then assessed.RESULTS: The 16S rDNA sequencing results showed that the β-diversity of the gut microbiota was significantly different between the IDD and control groups, with distinct abundance levels of dominant genera. Moreover, 59 metabolites were significantly upregulated and 91 were downregulated in IDD rabbits versus the controls. The KEGG enrichment analysis revealed that the top pathways remarkably impacted by IDD were tyrosine metabolism, amino sugar and nucleotide sugar metabolism, benzoate degradation, ABC transporters, ascorbate and aldarate metabolism, pantothenate and CoA biosynthesis, and pyrimidine metabolism. The correlation analysis revealed that DL-tyrosine and N-acetylmuramic acid were associated with multiple differential bacterial genera, including Helicobacter and Vibrio, which may play important roles in the process of IVD degeneration.CONCLUSION: Our findings revealed that IDD altered gut microbiota and fecal metabolites in a rabbit model. The correlation analysis of microbiota and metabolome provides a deeper understanding of IDD and its possible etiopathogenesis. These results also provide a direction and theoretical basis for the clinical application of fecal transplantation, probiotics, and other methods to regulate gut microbiota in the treatment of LBP caused by IDD.PMID:38169417 | DOI:10.1186/s13018-023-04486-x