Biology subjects

Thomas, D. G.

Publications and source records attributed to Thomas, D. G..

5 recordsLinked to original sources

bioRxiv2026

Effect of Lactobacillus postbiotic supplementation on intestinal permeability, nutrient digestibility, and gut microbial and metabolic profiles in aging cats

Aging in cats is associated with declining nutrient digestibility and increased intestinal permeability, but evidence supporting microbiome-targeted interventions in older cats remains limited. We investigated whether daily supplementation with the Lactobacillus-derived postbiotic LB fermentate HF (LBHF) affected intestinal permeability, apparent total tract digestibility, gut microbiome composition, and fecal and plasma metabolomic profiles in older cats. Twenty cats aged 7.7-13.8 years were enrolled in a blinded, placebo-controlled crossover trial comprising two 29-day treatment periods separated by a 28-day washout; 18 cats completed both periods. Intestinal permeability was the primary endpoint, while nutrient digestibility, microbiome composition, and metabolomic profiles were secondary endpoints. LBHF did not affect intestinal permeability or absorptive capacity relative to placebo, although intestinal permeability was positively associated with age. Overall nutrient digestibility was higher during LBHF treatment, with the clearest endpoint-specific evidence observed for protein digestibility. LBHF was associated with a non-significant overall increase in Shannon diversity and a reduction in the relative abundance of Streptococcus lutetiensis. The increase in Shannon diversity was significant only in cats receiving placebo followed by LBHF, indicating a treatment-sequence-dependent response. Thirty-three plasma and 29 fecal metabolites showed significantly different changes during LBHF treatment compared with placebo. Plasma metabolites generally showed more positive changes during LBHF treatment, whereas most associated fecal metabolites showed more negative changes. Sequence-stratified microbiome and metabolome responses differed substantially, suggesting possible period, treatment-order, or carryover effects. Overall, LBHF did not improve intestinal permeability but was well tolerated and improved nutrient digestibility, particularly protein digestibility, while producing modest and sequence-dependent microbiome and metabolome responses. These findings suggest that the effects of LBHF in healthy older cats may relate more strongly to digestive efficiency and host metabolic responses than to intestinal permeability.

microbiology↗

bioRxiv2026

Lipid mobilization establishes metabolic tolerance and prevents autonomic collapse in infection

Survival during infection depends on both pathogen clearance and the ability to tolerate infection-induced physiological changes. Metabolic adaptations are a central component of this tolerance, but the mechanisms underlying these responses remain incompletely defined. Here, we identify white adipose tissue (WAT) lipolysis as a central regulator of metabolic tolerance to infection. In patients with sepsis, higher circulating non-esterified fatty acid (NEFA) levels were associated with reduced mortality. In mouse models of polymicrobial sepsis, infection induced robust adipose lipolysis and increased circulating NEFAs. Genetic ablation of adipose triglyceride lipase (ATGL) in adipose tissue impaired lipolysis, leading to hypothermia, bradycardia, and increased mortality without altering immune cell populations or pathogen burden, consistent with a defect in tolerance rather than resistance. Mechanistically, lipolysis-derived NEFAs, but not glycerol, were required for protection, as restoring circulating NEFAs rescued autonomic stability and survival in adipose tissue ATGL-deficient mice. Infection-induced lipolysis was redundantly regulated and did not depend on any single upstream signaling pathway. Both pharmacologic activation of lipolysis using a {beta}3-adrenergic agonist and exogenous fatty acid supplementation increased circulating NEFAs, improved survival, and promoted tolerance in mice. Consistent with these findings, analysis of real-world electronic health record data demonstrated that septic patients receiving FDA-approved {beta}3-adrenergic agonists had reduced mortality or hospice discharge in a propensity-matched cohort. Together, these results identify WAT lipolysis and circulating fatty acids as key mediators of tolerance to infection and support a therapeutic strategy based on repurposing clinically available {beta}3-adrenergic agonists to improve outcomes in sepsis. One Sentence SummaryWhite adipose tissue lipolysis promotes metabolic tolerance to infection through circulating fatty acids and is associated with improved survival in sepsis

physiology↗

bioRxiv2024

Effects of Concussion on the Relative Contributions of Sensorimotor Memories during Adaptation to Unpredictable Spring-Like Loads

We examined the extent to which concussion impacts how implicit sensorimotor memories are used to compensate for changes in hand-held loads during goal-directed reaching. Recently concussed individuals performed computerized cognition tests and a robotic test of sensorimotor adaptation on three occasions: as soon as possible after injury; after clearance to return to activity; three months after injury. Non-concussed individuals (controls) were tested at inter-session intervals mimicking concussed group intervals. During robotic testing, subjects grasped the handle of a horizontal planar robot while reaching repeatedly to a target. The robot exerted spring-like forces that changed unpredictably between trials; this allowed us to estimate contributions of implicit sensorimotor memories to trial-by-trial performance by fitting a computational model to the time series of reach errors and robot forces. Symptom severity varied considerably within the concussed group at the first session. Computerized cognition tests revealed longer reaction times in the concussed group relative to control group in Session 1 only. Concussed subjects likewise had slower reaction time in the reaching task during the first but not later sessions. Computational modeling found abnormally high values of effective limb compliance in concussed individuals relative to the control group in the first session only, but did not find group differences in how sensorimotor memories contribute to reach adaptation in any session. Analysis of control group models identified a practice effect affecting the memory coefficients that may have masked initial effects of concussion on how implicit memories contribute to sensorimotor adaptation. Although a practice effect and a heterogeneous concussed cohort preclude strong conclusions, our findings suggest procedural improvements that may decrease the robotic tests sensitivity to practice effects and increase its sensitivity to concussion-related changes in how implicit memories contribute to sensorimotor adaptation to unpredictable hand-held loads during reaching.

neuroscience↗

bioRxiv2023

Contribution of Implicit Memory to Adaptation of Movement Extent During Reaching Against Unpredictable Spring-Like Loads: Insensitivity to Intentional Suppression of Kinematic Performance

We examined the extent to which intentionally underperforming a goal-directed reaching task impacts how memories of recent performance contribute to sensorimotor adaptation. Healthy human subjects performed computerized cognition testing and an assessment of sensorimotor adaptation wherein they grasped the handle of a horizontal planar robot while making goal-directed out-and-back reaching movements. The robot exerted forces that resisted hand motion with a spring-like load that changed unpredictably between movements. The robotic test assessed how implicit and explicit memories of sensorimotor performance contribute to the compensation for the unpredictable changes in the hand-held load. After each movement, subjects were to recall and report peak movement extent from the previous trial. Subjects performed the tests under two counterbalanced conditions: one where they performed with their best effort, and one where they intentionally suppressed performance. Results from the computerized cognition tests confirmed that subjects understood and complied with task instructions. When suppressing performance during the robotic assessment, subjects demonstrated marked changes in reach precision, time to capture the target, and reaction time. We fit a set of limited memory models to the data to identify how subjects used implicit and explicit memories of recent performance to compensate for the changing loads. In both sessions, subjects used implicit, but not explicit, memories from the most recent trial to adapt reaches to unpredictable spring-like loads. Subjects did not "give up" on large errors, nor did they discount small errors deemed "good enough." Although subjects clearly suppressed kinematic performance (response timing, movement variability, and self-reporting of reach error), the relative contributions of sensorimotor memories to trial-by-trial variations in task performance did not differ significantly between the two testing conditions. We conclude that intentional performance suppression had minimal impact on how implicit sensorimotor memories contribute to adaptation of unpredictable mechanical loads applied to the hand.

neuroscience↗

bioRxiv2020

Contributions of Implicit and Explicit Memories to Sensorimotor Adaptation of Movement Extent During Goal-Directed Reaching

We examined how explicit memory of kinematic performance contributes to motor adaptation during goal-directed reaching. Twenty subjects grasped the handle of a horizontal planar robot that rendered spring-like resistance to movement. Subjects made rapid "out-and-back" reaches to capture a remembered visual target at the point of maximal reach extent. The robots resistance changed unpredictably between reaches, inducing target capture errors that subjects attempted to correct from one trial to the next. The subjects performed four sets of trials. Three were performed without concurrent visual cursor feedback of hand motion. Two of these required self-assessment of performance between trials, whereby subjects reported peak reach extent on the most recent trial. This was done by either moving a cursor on a horizontal display (visual self-assessment), or by moving the robots handle back to the recalled location (proprioceptive self-assessment). Two control conditions were performed either without or with concurrent visual cursor feedback of hand motion. We analyzed movement kinematics and used regression analyses to quantify the extent to which prior reach errors and explicit memories of prior performance contribute to subsequent reach performance. Consistent with prior reports, providing concurrent visual feedback of hand motion increased reach accuracy and reduced the impact of past performance errors on future performance, relative to the no-vision control condition. By contrast, we found no impact of interposed self-assessment on reach kinematics or on how prior target capture errors influence subsequent reach performance. Self-assessments were biased toward the remembered target location, differing markedly from actual reach performances. Including self-assessments as explicit memory of performance in the regression analyses did not improve model predictive accuracy. Therefore, we conclude that explicit memories of prior kinematic performance do not contribute to implicit sensorimotor adaptation of movement extent.

neuroscience↗