Frontiers in Physiology最新文献

{"title":"Deployability of machine-learning prediction models in elite and high-level team sports: a task-specific systematic review.","authors":"Zhiyu Guan, Zicheng Jin, Chuangui Mao, Weiguo Liu, Jie Ren","doi":"10.3389/fphys.2026.1920214","DOIUrl":"10.3389/fphys.2026.1920214","url":null,"abstract":"<p><p>Machine-learning models are increasingly used for match forecasting and athlete monitoring in elite and high-level team sports, but high reported performance does not necessarily indicate readiness for real-world use. This systematic review evaluated whether models were developed and tested under conditions compatible with their intended decision time. Eight databases were searched, with searches completed by 12 July 2026. Eighty reports representing 77 studies contributed 87 analysis units: 55 Core, 23 post-event or high-leakage Comparators, and nine Boundary units. All 87 units were assessed for deployable prediction validity (DPV) across six domains, and 78 Core or Comparator units were also assessed with PROBAST. Amongst Core units, 26/55 (47.3%) were rated at least Moderate, including five Moderate-to-strong and 21 Moderate units. Pre-adjudication agreement for the overall DPV classification was 85/87 (97.7%; κ = 0.968; linearly weighted κ = 0.978), whilst domain-level exact agreement ranged from 75/87 to 87/87. In <i>post hoc</i> sensitivity analyses, 19/55 Core units met the primary DPV threshold and had Sufficient validation; 14/55 met the primary threshold and had at least partial evidence of predictive reliability or probability-quality; and 9/55 met the primary threshold and both additional conditions. PROBAST risk of bias was High for 56/78 units, Unclear for 21/78, and Low for one. The main limitations were evaluation designs that did not adequately reflect intended future use and limited assessment of predictive reliability. Overall, the evidence supports selective methodological readiness rather than general deployability, with different requirements for pre-game, in-game, and athlete-monitoring applications.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD420261425179 <b>, identifier CRD420261425179.</b></p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1920214"},"PeriodicalIF":4.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do strategically demanding sports shape hand function alike? Distinct profiles of dexterity and grip strength in basketball and badminton athletes.","authors":"Xinpeng Gao, Jinlong Hou, Chengzhe Du, Yanan Gao, Fei Kong, Ming Li","doi":"10.3389/fphys.2026.1940944","DOIUrl":"10.3389/fphys.2026.1940944","url":null,"abstract":"<p><strong>Purpose: </strong>Long-term participation in strategic sports may enhance hand dexterity and cognitive function, but sport-specific differences in manual control, force production, and cognition remain unclear. This study compared hand dexterity, grip strength, and cognitive performance among basketball athletes, badminton athletes, and non-athletes.</p><p><strong>Methods: </strong>This cross-sectional observational study included 90 right-handed participants (6 females, 84 males; mean age 20.57 ± 1.64 years) divided into the basketball athlete group (BAG), badminton athlete group (BmAG), and non-athlete controls (NCG). Participants completed the Purdue Pegboard Test (PPT), Grooved Pegboard Test (GPT), handgrip strength test (HD), Montreal Cognitive Assessment (MoCA), and Stroop Color-Word Test (SCWT). Results: Both BAG and BmAG outperformed NCG in PPT dominant-hand scores, combined task scores, GPT completion speed, MoCA scores, and SCWT word reading (all P < 0.05). BmAG also showed superior PPT non-dominant-hand performance, bimanual coordination, and total scores compared with NCG, and better bimanual coordination than BAG (BmAG vs. NCG: P < 0.001, d = 0.96; BmAG vs. BAG: P = 0.033, d = 0.66). BAG demonstrated greater dominant-hand grip strength than NCG (P = 0.007, d = 0.90), whereas BmAG did not. No group differences were found in SCWT inhibitory control or cognitive flexibility.</p><p><strong>Conclusion: </strong>Badminton participation was associated with superior fine motor control and bimanual coordination, whereas basketball participation was associated with greater dominant-hand grip strength. Both athletic groups showed better selected manual and cognitive outcomes than NCG. However, the cross-sectional, male-skewed sample cannot establish causality, and the MoCA findings should be interpreted cautiously because of its ceiling effect in healthy young participants. Longitudinal or intervention studies are warranted. After Holm-Bonferroni correction for multiple outcomes, the group effects for PPT non-dominant-hand performance, dominant-hand grip strength, and Stroop word reading did not remain significant and are therefore interpreted as exploratory.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1940944"},"PeriodicalIF":4.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic graph vector autoregression for characterizing cardiac electromechanical dynamics during incremental exercise from the joint phase space of electrocardiogram and phonocardiogram.","authors":"Xiaohong Ye, Qiang Lu, Qianyu Lin","doi":"10.3389/fphys.2026.1946312","DOIUrl":"https://doi.org/10.3389/fphys.2026.1946312","url":null,"abstract":"<p><p>Abnormal cardiac electromechanical coupling (cEMC) is associated with exercise-induced arrhythmias, yet monitoring cEMC during unrestricted movement remains challenging. While electrocardiogram (ECG) and phonocardiogram (PCG) recordings provide indirect measures of cardiac electrical and mechanical activity, each represents only a one-dimensional scalar observation of the cardiac system, and the system's latent state-space dynamics response to exercise intensity remains inaccessible. Therefore, this study employs Takens' delayed embedding phase-space reconstruction method to reconstruct the latent state trajectories and then combines them into a joint ECG-PCG phase space. Building on this representation, this study proposes dynamic graph vector autoregression (DG-VAR), a data-driven analytical approach for characterizing latent cEMC from the joint phase space of ECG and PCG during exercise. Benchmarking with an open-access database demonstrated that DG-VAR achieved the highest performance in predicting the joint phase space of ECG and PCG during exercise. The method yielded an average root mean square error (RMSE) of 0.0186 and mean absolute percentage error (MAPE) of 7.76 for ECG phase space predictions, and an average RMSE of 0.0085 and MAPE of 4.45 for PCG phase space predictions. Furthermore, matrix-derived parameters, including stationarity, coupling strength, and dynamic graph topology, showed significant correlations with cardiac electromechanical intervals. Analysis of these parameters revealed an intensity-dependent regulatory pattern in cardiac electromechanical dynamics: forward electromechanical coupling increases monotonically, the feedback mechanism rises initially and then stabilizes, and the network dynamics topology evolves towards a state of greater density and smoothness. This non-invasive, label-free, data-driven analytical framework offers a novel, physiologically interpretable approach to dynamic monitoring of exercise-induced cEMC responses.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1946312"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of functional training on linear sprint and change-of-direction performance in soccer players: a systematic review and meta-analysis.","authors":"Hongyu Yang, Ya Lan, Yu Chen, Shang Zeng","doi":"10.3389/fphys.2026.1951674","DOIUrl":"https://doi.org/10.3389/fphys.2026.1951674","url":null,"abstract":"<p><strong>Background: </strong>Functional training is increasingly incorporated into soccer conditioning; however, its effects on linear sprint and change-of-direction (COD) performance remain unclear. This systematic review and meta-analysis evaluated the effects of structured functional training on linear sprint and directional-change performance in soccer players.</p><p><strong>Methods: </strong>PubMed, Web of Science, Embase, SPORTDiscus via EBSCOhost, Scopus, and the Cochrane Library were searched from database inception to 6 July 2026. Randomized controlled trials comparing structured functional training with usual soccer training, no additional training, or other non-functional training conditions were included. Pooled effects were calculated as Hedges' g with 95% confidence intervals (CIs) using random-effects models. Exploratory subgroup analyses were conducted according to intervention duration, weekly training frequency, and sprint distance. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.</p><p><strong>Results: </strong>Ten randomized controlled trials involving 260 soccer players were included. Functional training significantly improved pre-planned COD performance (nine trials; n = 240; Hedges' g = -0.72, 95% CI -1.23 to -0.22; p = 0.005; I² = 71%) and linear sprint performance (seven trials; n = 164; Hedges' g = -1.00, 95% CI -1.54 to -0.46; p = 0.0003; I² = 61%). Leave-one-out sensitivity analyses showed that the direction and statistical significance of both pooled effects were retained after exclusion of individual studies, although the magnitude of the COD and sprint estimates was influenced by Zhao et al. and Doungchan et al., respectively. No statistically significant between-subgroup differences were identified according to intervention duration, weekly training frequency, or sprint distance.</p><p><strong>Conclusion: </strong>Structured functional training may improve linear sprint and pre-planned COD performance in soccer players. However, the magnitude of the pooled effects should be interpreted cautiously because of between-study heterogeneity, the influence of individual studies, and the limited evidence base. Current evidence is insufficient to establish an optimal training prescription or to extrapolate these findings to reactive agility or match performance.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PR, identifier CRD420261441220.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1951674"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cadherin as a potential novel regulator of intestinal inflammation and fibrosis.","authors":"Yan Wang, Ankita Prasad, Weiwei Liu, Jyotsna Chandra, Atif Zafar, Nayden G Naydenov, Pranab K Mukherjee, Andrei I Ivanov, Florian Rieder","doi":"10.3389/fphys.2026.1946754","DOIUrl":"10.3389/fphys.2026.1946754","url":null,"abstract":"<p><p>T-cadherin (T-cad) is a non-canonical member of the cadherin superfamily with a distinguished structure of its glycosylphosphatidylinositol (GPI) anchor instead of transmembrane and cytoplasmic domains. This lends unique properties to and equips T-cad with dynamic mobility within the plasma membrane and extensive lateral interactions with signaling partners. Beyond its role as an adhesion molecule forming homophilic interactions, T-cad functions as a receptor for adiponectin and low-density lipoprotein (LDL), therefore playing an important role in regulating cellular processes such as proliferation, differentiation, and migration. These properties underscore its critical involvement in physiological and pathological processes, including central nervous system development, cancer progression, and cardiovascular disease. However, the role of T-cad in intestinal inflammation, injury, and fibrosis remains underexplored. This review highlights the structural and functional characteristics of T-cad, its binding partners, its expression and functions in various types of cells, tissues and organs, and its roles in health and disease. This review also speculates on its potential involvement in intestinal inflammation, particularly in stricturing Crohn's disease.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1946754"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative endpoint and reconstructed 500-m energy-system contributions from individualized pacing-matched trials in 2000-m rowing ergometry.","authors":"Jiashi Lin, Xiaoning Ma, Caoan Yuan, Lei Yi","doi":"10.3389/fphys.2026.1840466","DOIUrl":"https://doi.org/10.3389/fphys.2026.1840466","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the accuracy with which 500-, 1000-, and 1500-m endpoint trials reproduced each rower's individualized 2000-m pacing template, estimate cumulative energy-system contributions at 500, 1000, 1500, and 2000 m, and reconstruct contributions across four successive 500-m segments.</p><p><strong>Methods: </strong>Twelve trained male provincial-team rowers completed a 2000-m all-out rowing-ergometer reference trial to establish individualized cumulative time, mean power, and mean stroke-rate targets, followed by pacing-matched 500-, 1000-, and 1500-m endpoint trials. Pacing-replication accuracy was evaluated using achieved-minus-target bias, MAE, MAPE, concordance, and Bland-Altman limits of agreement. Energy-system contributions were estimated indirectly using the PCr-La-O₂ framework. Cumulative endpoints and within-rower reconstructed 500-m segments were analyzed separately using repeated-measures analyses with Holm-adjusted comparisons.</p><p><strong>Results: </strong>At 500, 1000, and 1500 m, time MAE was 0.050, 0.092, and 1.258 s; power MAE was 0.667, 0.917, and 5.083 W; and stroke-rate MAE was 0.750, 0.396, and 0.359 spm, respectively. Corresponding MAPE values were 0.053-0.431% for time, 0.157-1.339% for power, and 1.239-2.483% for stroke rate. No stable group-level systematic bias was detected after Holm adjustment, although statistical equivalence was not tested. Reconstruction showed a higher estimated phosphagen contribution during 0-500 m, glycolytic contribution concentrated mainly within the first 1000 m, and a higher aerobic contribution after the opening segment. No robust segmental difference in total estimated contribution was concluded.</p><p><strong>Conclusions: </strong>Individualized known-endpoint trials can closely reproduce a rower's 2000-m pacing template while providing endpoint-specific post-exercise inputs for cumulative indirect energy-system estimation. Within-rower reconstruction offers a transparent way to describe successive 500-m energetic patterns alongside actual kinematics, but these reconstructed segments should not be interpreted as direct physiological measurements of continuous race phases or as a validated training prescription.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1840466"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute neuromuscular and metabolic responses to complex training with blood flow restriction: effects of arterial occlusion pressure on post-activation performance enhancement.","authors":"Xiaohan Wang, Yin Yu, Jiayue Cui, Simin Lin, Qihao Sun, Bocheng Guo","doi":"10.3389/fphys.2026.1932866","DOIUrl":"10.3389/fphys.2026.1932866","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined the acute effects of complex training (CT) with blood flow restriction (BFR) on countermovement jump (CMJ) performance, lower<b>-</b>limb muscle activation, and blood lactate (BLa) concentration in trained male collegiate athletes. It also aimed to identify the arterial occlusion pressure (AOP) level and recovery time window that produced the most favorable post<b>-</b>activation performance enhancement (PAPE) response.</p><p><strong>Methods: </strong>Using a randomized crossover design, twelve trained male collegiate athletes completed four experimental conditions: traditional CT and CT<b>-</b>BFR at 60%, 70%, and 80% AOP. CMJ performance (VJH: vertical jump height and RPP: relative peak power), muscle activation (RMS: root mean square and MF: median frequency), and BLa were assessed before the intervention and at 4, 8, 12, and 16 min following each protocol.</p><p><strong>Results: </strong>Traditional CT also induced significant changes in selected variables at specific recovery time points. However, the 70% AOP condition showed more consistent improvements among the tested conditions. Under 70% AOP, CMJ performance improved at 8 min, with significant increases in VJH (<i>p</i> < 0.05, ES = 0.37) and RPP (<i>p</i> < 0.05, ES = 0.94). RPP also remained elevated at 12 min (<i>p</i> < 0.05, ES = 0.77). This condition also showed more consistent sEMG responses, with increased RMS in the RF, VM, VL, and BF at 8 min, and changes in the VM and VL at 12 min (<i>p</i> < 0.05). MF changes were mainly observed in the VM and VL. In contrast, the 60% and 80% AOP conditions showed less consistent improvements in CMJ performance and muscle activation. BLa showed a significant time effect and AOP × time interaction, increasing markedly after the intervention, peaking at 4 min, and then progressively declining during recovery (<i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>CT-BFR at 70% AOP showed a relatively favorable acute response among the tested conditions, especially for CMJ performance and thigh muscle activation during the 8-12 min recovery window. These findings provide preliminary evidence that 70% AOP may be a potentially suitable pressure level for CT<b>-</b>BFR based on the acute responses observed during PAPE based warm<b>-</b>up protocols.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1932866"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Assessment and monitoring of human movement, volume II.","authors":"Daniel López-Plaza, Giuseppe Annino, Cristian Romagnoli","doi":"10.3389/fphys.2026.1995658","DOIUrl":"https://doi.org/10.3389/fphys.2026.1995658","url":null,"abstract":"","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1995658"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond vitamin D: integrating nuclear receptor signaling networks in periodontal health and disease.","authors":"Yujia Chen, Liancheng Guan, Qian Li, Yihui Chai, Jie Gao","doi":"10.3389/fphys.2026.1969566","DOIUrl":"https://doi.org/10.3389/fphys.2026.1969566","url":null,"abstract":"<p><p>Vitamin D receptor (VDR) signaling has been studied extensively in periodontology, yet the broader nuclear receptor superfamily remains underexplored. We examined the roles of four nuclear receptor family members: VDR, peroxisome proliferator-activated receptor gamma (PPAR-γ), retinoid X receptor alpha (RXR-α), and farnesoid X receptor (FXR) in periodontal health and disease across the continuum from gingival health through gingivitis to periodontitis. However, most functional and mechanistic evidence is derived from established or experimental periodontitis, whereas evidence from periodontal health and gingivitis remains limited. VDR, PPAR-γ, and FXR have been associated with periodontal immune and bone responses through distinct but intersecting pathways. VDR induces cathelicidin and modulates RANKL/OPG expression. PPAR-γ suppresses NF-κB-mediated cytokine production and promotes M2 macrophage polarization. FXR agonists reduce osteoclastogenesis while enhancing osteoblast differentiation in rodent periodontitis models. In general nuclear receptor biology, RXR-α is a heterodimerization partner for VDR, PPAR-γ, and FXR and may represent a putative integrative node in periodontal signaling. However, the direction and magnitude of RXR-α expression changes remain inconsistent, and the effects of RXR ligand activation on VDR and PPAR-γ transcriptional activity in periodontal tissues remain to be established. Major gaps remain: human data on PPAR-γ and FXR are scarce, localized nuclear receptor activation has not advanced to clinical trials, and nuclear receptor interactions with periodontal biofilms remain uncharacterized. A network-centered framework prioritizing RXR-mediated heterodimerization, localized ligand delivery, nuclear receptor-selective modulators, and genotype-guided supplementation may help define future research directions, but these applications require further validation.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1969566"},"PeriodicalIF":4.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic elevation of gut derived <i>p</i>-cresol during one year in space: implications for brain, heart, bone, liver and microbiome in astronauts.","authors":"Michael A Schmidt, Caleb M Schmidt, Julian C Schmidt, Cem Meydan, Evan E Afshin, Eliah G Overbey, JangKeun Kim, Ruth Subhash Singh, Afshin Beheshti, Christopher E Mason","doi":"10.3389/fphys.2026.1878680","DOIUrl":"https://doi.org/10.3389/fphys.2026.1878680","url":null,"abstract":"<p><strong>Introduction: </strong>We observed the elevation of <i>p</i>-cresol in the untargeted metabolome of the multiomics portion of the NASA Twins Study of One Year in Space. <i>p</i>-Cresol is a uremic and neurotoxin that is produced via the metabolism of dietary tyrosine by gut bacteria. Intestinally produced <i>p</i>-cresol is absorbed into systemic circulation where it exerts its adverse metabolic effects and drives phenotypic changes relevant to astronauts, including the brain, heart, bone, liver, kidney, and colon.</p><p><strong>Methods: </strong>A pair of monozygotic twins were studied for 25 months, during which one subject spent 340 days aboard the International Space Station (ISS), while his identical twin remained on Earth. Molecular analyses included genome, epigenome, transcriptome, proteome, metabolome, immunome, and microbiome. Our metabolite feature extraction was focused on plasma <i>p</i>-cresol (<i>p</i>-cresyl sulfate [pCS] and <i>p</i>-cresol glucuronide [pCG]), along with associated biological dynamics that govern <i>p</i>-cresol production and metabolism.</p><p><strong>Results: </strong>Significance was observed for pCG when comparing Post-flight vs. Inflight (adj p = 0.016). pCS values were significantly altered Post-flight vs. Inflight (adj p = 0.002) and Post-flight vs. Late-flight (adj p = 0.037). pCS values for Early-flight vs. Pre-flight approached significance (adj p = 0.08). In alignment with elevated plasma <i>p</i>-cresol values at certain stages of spaceflight, we found an increase in count-normalized abundance (raw reads) for the major <i>p</i>-cresol producer <i>Clostridioides difficile</i> in TW (Flight) vs. HR (Ground) for Post-flight, Inflight, and Overall (adj p = 0.014, adj p = 0.0006, and adj p = 2.02x10¯⁵, respectively). Concomitantly, we observed a significant increase in count-normalized abundance for another of the major <i>p</i>-cresol producers <i>Olsenella uli</i> in TW vs. HR for Post-flight, Inflight, and Overall (adj p = 0.0045, adj p = 0.00043, adj p = 0.0016, respectively), including Interaction for Inflight vs. Pre-flight (adj p = 0.028).</p><p><strong>Discussion: </strong>We observed an elevation of <i>p</i>-cresol during one year in space, which may have significant implications for astronaut health and performance. Molecular findings and <i>p</i>-cresol countermeasure candidates are discussed. We also explore the process from untargeted molecular feature extraction to description of biological meaning, to new hypothesis generation, to plausible countermeasure development for human spaceflight.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1878680"},"PeriodicalIF":4.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}