Clinical Commentary: A Criteria-Based Testing Protocol for Return to Sport Post Hip Arthroscopy for Impingement.

Overall, 84%-87% of athletes will return to sport following hip arthroscopy; however, some literature suggests that only 57% of athletes return to their preinjury level, and only 16.9% report optimal performance. This discrepancy may be due to a lack of consistency within the definition of return to sport as well as a lack of consistency within rehabilitation programs when determining return to sport readiness. Athletes who are returning to sport must demonstrate adequate range of motion, strength, and the ability to perform multi-directional movements without the risk of reinjury. There has yet to be a comprehensive, criteria-based, return to sport testing protocol that utilizes objective measures to ensure athletes are ready for return to sport. The goal of the authors was to create a criteria-based testing protocol for return to sport following hip arthroscopy utilizing components best supported in the literature. The following parameters were identified as key areas to assess for within a return to sport testing protocol: range of motion, strength, functional testing, self-reported outcomes including psychological readiness and time. The purpose of this clinical commentary is to propose a criteria-based testing protocol to be used following hip arthroscopy for impingement from early rehabilitation through return to previous level of sport. Criteria are presented clearly to promote objective progression through rehabilitation while still being mindful of the biological healing time required for safe and efficient progression. It is the authors' hope that in identifying and establishing a criteria-based testing protocol a higher percentage of athletes will be able to return to sport. Level of Evidence: 5.

VH2+ Antigen-Experienced B Cells in the Cerebrospinal Fluid Are Expanded and Enriched in Pediatric Anti-NMDA Receptor Encephalitis.

Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti-NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti-NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti-NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti-NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti-NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti-NMDAR-AE patients may be relevant for clinical diagnosis and treatment.

Prostatic proliferative inflammatory atrophy: welcome to the club†.

Single-cell RNA sequencing studies in the human prostate have defined a population of epithelial cells with transcriptional similarities to club cells in the lung. However, the localization of club-like cells in the human prostate, and their relationship to prostate cancer, is poorly understood. In a new article in The Journal of Pathology, RNA in situ hybridization was used to demonstrate that club cell markers are expressed in luminal cells adjacent to inflammation in the peripheral zone of the human prostate, where prostate cancer tends to arise. These club-like cells are commonly found in proliferative inflammatory atrophy (PIA) lesions and express markers consistent with an intermediate epithelial cell-type. Future studies will be needed to understand the functional role of club-like cells in human prostate inflammation, regeneration, and disease. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Neuron-binding antibody responses are associated with Black ethnicity in multiple sclerosis during natalizumab treatment.

Multiple sclerosis is an inflammatory degenerative condition of the central nervous system that may result in debilitating disability. Several studies over the past twenty years suggest that multiple sclerosis manifests with a rapid, more disabling disease course among individuals identifying with Black or Latin American ethnicity relative to those of White ethnicity. However, very little is known about immunologic underpinnings that may contribute to this ethnicity-associated discordant clinical severity. Given the importance of B cells to multiple sclerosis pathophysiology, and prior work showing increased antibody levels in the cerebrospinal fluid of Black-identifying, compared to White-identifying multiple sclerosis patients, we conducted a cohort study to determine B cell subset dynamics according to both self-reported ethnicity and genetic ancestry over time. Further, we determined relationships between ethnicity, ancestry, and neuron-binding IgG levels. We found significant associations between Black ethnicity and elevated frequencies of class-switched B cell subsets, including memory B cells; double negative two B cells; and antibody-secreting cells. The frequencies of these subsets positively correlated with West African genetic ancestry. We also observed significant associations between Black ethnicity and increased IgG binding to neurons. Our data suggests significantly heightened T cell-dependent B cell responses exhibiting increased titres of neuron-binding antibodies among individuals with multiple sclerosis identifying with the Black African diaspora. Factors driving this immunobiology may promote the greater demyelination, central nervous system atrophy and disability more often experienced by Black-, and Latin American-identifying individuals with multiple sclerosis.

Neuronal binding by antibodies can be influenced by low pH stress during the isolation procedure.

Low pH stress and its influence on antibody binding is a common consideration among chemists, but is only recently emerging as a consideration in Immunological studies. Antibody characterizations in Multiple Sclerosis (MS), an autoimmune disease of the Central Nervous System (CNS) has revealed that antibodies in the cerebrospinal fluid (CSF) of patients with Multiple Sclerosis bind to myelin-related and non-myelin antigen targets. Many laboratories have used molecular biology techniques to generate recombinant human antibodies (rhAbs) expressed by individual B cells from healthy donors and patients with systemic autoimmune disease to identify antigen targets. This approach has been adapted within the Neuroimmunology research community to investigate antigen targets of individual B cells in the CSF of MS patients. Our laboratory determines which antibodies to clone based on their immunogenetics and this method enriches for cloning of rhAbs that bind to neurons. However, newer technologies to assist in purification of these rhAbs from culture supernatants use an acidic elution buffer which may enhance low pH stress on the antibody structure. Our laboratory routinely uses a basic elution buffer to purify rhAbs from culture supernatants to avoid low pH stress to the antibody structure. Our goal was to investigate whether acidic elution of our rhAbs using Next Generation Chromatography would impact the rhAbs' ability to bind neurons. The limited data presented here for two neuron-binding rhAbs tested indicated that acidic elution buffers used during rhAb purification impacted the ability of rhAbs with low CDR3 charge to maintain binding to neuronal targets. Reproducibility in a larger panel of rhAbs and factors underlying these observations remain untested.

Inflammasome-Mediated Neuronal-Microglial Crosstalk: a Therapeutic Substrate for the Familial C9orf72 Variant of Frontotemporal Dementia/Amyotrophic Lateral Sclerosis.

Intronic G4C2 hexanucleotide repeat expansions (HRE) of C9orf72 are the most common cause of familial variants of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). G4C2 HREs in C9orf72 undergo non-canonical repeat-associated translation, producing dipeptide repeat (DPR) proteins, with various deleterious impacts on cellular homeostasis. While five different DPRs are produced, poly(glycine-arginine) (GR) is amongst the most toxic and is the only DPR to accumulate in the associated clinically relevant anatomical locations of the brain. Previous work has demonstrated the profound effects of a poly (GR) model of C9orf72 FTD/ALS, including motor impairment, memory deficits, neurodegeneration, and neuroinflammation. Neuroinflammation is hypothesized to be a driving factor in the disease course; microglia activation is present prior to symptom onset and persists throughout the disease. Here, using an established mouse model of C9orf72 FTD/ALS, we investigate the contributions of the nod-like receptor pyrin-containing 3 (NLRP3) inflammasome in the pathogenesis of FTD/ALS. We find that inflammasome-mediated neuroinflammation is increased with microglial activation, cleavage of caspase-1, production of IL-1ß, and upregulation of Cxcl10 in the brain of C9orf72 FTD/ALS mice. Excitingly, we find that genetic ablation of Nlrp3 significantly improved survival, protected behavioral deficits, and prevented neurodegeneration suggesting a novel mechanism involving HRE-mediated induction of innate immunity. The findings provide experimental evidence of the integral role of HRE in inflammasome-mediated innate immunity in the C9orf72 variant of FTD/ALS pathogenesis and suggest the NLRP3 inflammasome as a therapeutic target.

Update and Extension of Release Criteria for Canine 117m Sn Treatments.

ABSTRACT: Tin-117 m ( 117m Sn) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The internal conversion and Auger electrons emitted by the 117m Sn provide the therapeutic effect. Sn-117 m also emits x rays and gamma rays, of which the most significant is 158.6 keV. Accurate information regarding the interactions of a person with a treated dog is needed to determine the person's total dose and thus regulatory compliance; i.e., a time and motion study. Prior studies have characterized the radiation field emitted by a treated dog, determined the effective dose rates to a person based on those radiation fields, and evaluated dog-human interactions. These studies have been tied together to calculate the prospective dose to the owner of a treated dog. The behavior modifications needed to comply with public dose limits were identified, and a template for written instructions limiting dose was developed. Further calculations based on the written instructions were made to determine the necessary duration of the instructions. The result is guidance that may be used by veterinary practitioners to release treated dogs in accordance with the public dose limits.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

External Radiation Dose to Owners of Canines Treated with ( 117m Sn) Radiosynoviorthesis for Osteoarthritis.

ABSTRACT: A novel device in the veterinary market uses a colloid containing radioactive 117m Sn to treat osteoarthritis in the synovial joints of canines. The technique of injecting a radioisotope to restore synovia is referred to as radiosynoviorthesis. The outpatient canine procedure uses a maximum administration of 222 MBq of 117m Sn injected into one or more joints. Due to the 13.91 d half-life and 158.6 keV gamma output of 117m Sn, abiding by the annual public dose limit of 1 mSv is of primary regulatory concern. The therapy protocol starts with a pre-screening questionnaire to establish owner and animal behavior patterns. The questionnaire is used to determine the duration of written time and distance limitations post therapy. In this study, external radiation doses to owners were measured by providing optically stimulated luminescent dosimeters (OSLD) for up to 30 d post-treatment of the pet. Twelve owners were measured over various time frames at two licensed locations independent of each other. In one location, the average (OSLD) measured 0.029 mSv over a 14-d wear period. In the second location, the average (OSLD) measured 0.057 mSv over a 30-d wear period; both values were well below the recommended annual public dose. The overall average extrapolated external radiation dose was estimated at 0.092 mSv, while the maximum dose estimate was 0.25 mSv. The (OSLD) results and extrapolated owner doses provide reasonable assurance that the public dose limits will be met.

Development and validation of a reverse transcription real-time PCR assay for specific detection of PRRSGard vaccine-like virus.

Increasing use of modified live virus (MLV) vaccines presents challenges to interpret positive results of porcine reproductive and respiratory syndrome virus (PRRSV) screening PCR that can detect both wild-type and vaccine strains. Instead, vaccine-specific PCR provides a convenient tool to detect vaccine-like virus from a sample. Here we report the development and validation of a real-time RT-PCR specific for PRRSGard® , a newly available commercial PRRSV-2 MLV vaccine. Analytical specificity, sensitivity and diagnostic performance of PRRSGard PCR were evaluated and compared to a commercial PRRSV screening PCR (reference PCR). PRRSGard and reference PCRs did not cross-react with any of the 27 non-PRRSV swine pathogens. PRRSGard PCR did not cross-react with other PRRSV-2 vaccine viruses and 31 laboratory and field PRRSV-2 isolates representing various genetic lineages of PRRSV-2. PRRSGard and reference PCRs consistently detected up to 10-6 and 10-5 dilutions of PRRSGard vaccine virus, respectively. Based on testing serial dilutions of in vitro transcribed RNA, the 95% limit of detection of PRRSGard PCR was 16 genomic copies/reaction with CT cut-off value of 36 and 7 genomic copies/reaction with CT cut-off value of 37. Diagnostic performance of PRRSGard PCR was evaluated using 846 clinical samples (684 serum and 162 oral fluid samples). Compared to the reference screening PCR, diagnostic sensitivity, specificity and agreement of PRRSGard PCR were 95.34%, 98.85% and 97.52% with cut-off CT value of 36 and 98.14%, 96.56% and 97.16% with cut-off CT value of 37. In addition, PRRSGard PCR was able to detect PRRSGard vaccine virus in a sample even with the co-presence of another PRRSV strain. In summary, in contrast to a reference screening PCR that detects both vaccine and field PRRSV strains, PRRSGard PCR provides a convenient tool to specifically detect PRRSGard vaccine-like virus and to inform PRRSV vaccination protocols.

Artificial Selection on Microbiomes To Breed Microbiomes That Confer Salt Tolerance to Plants.

We develop a method to artificially select for rhizosphere microbiomes that confer salt tolerance to the model grass Brachypodium distachyon grown under sodium salt stress or aluminum salt stress. In a controlled greenhouse environment, we differentially propagated rhizosphere microbiomes between plants of a nonevolving, highly inbred plant population; therefore, only microbiomes evolved in our experiment, but the plants did not evolve in parallel. To maximize microbiome perpetuation when transplanting microbiomes between plants and, thus, maximize response to microbiome selection, we improved earlier methods by (i) controlling microbiome assembly when inoculating seeds at the beginning of each selection cycle; (ii) fractionating microbiomes before transfer between plants to harvest, perpetuate, and select on only bacterial and viral microbiome components; (iii) ramping of salt stress gradually from minor to extreme salt stress with each selection cycle to minimize the chance of overstressing plants; (iv) using two nonselection control treatments (e.g., nonselection microbial enrichment and null inoculation) that permit comparison to the improving fitness benefits that selected microbiomes impart on plants. Unlike previous methods, our selection protocol generated microbiomes that enhance plant fitness after only 1 to 3 rounds of microbiome selection. After nine rounds of microbiome selection, the effect of microbiomes selected to confer tolerance to aluminum salt stress was nonspecific (these artificially selected microbiomes equally ameliorate sodium and aluminum salt stresses), but the effect of microbiomes selected to confer tolerance to sodium salt stress was specific (these artificially selected microbiomes do not confer tolerance to aluminum salt stress). Plants with artificially selected microbiomes had 55 to 205% greater seed production than plants with unselected control microbiomes. IMPORTANCE We developed an experimental protocol that improves earlier methods of artificial selection on microbiomes and then tested the efficacy of our protocol to breed root-associated bacterial microbiomes that confer salt tolerance to a plant. Salt stress limits growth and seed production of crop plants, and artificially selected microbiomes conferring salt tolerance may ultimately help improve agricultural productivity. Unlike previous experiments of microbiome selection, our selection protocol generated microbiomes that enhance plant productivity after only 1 to 3 rounds of artificial selection on root-associated microbiomes, increasing seed production under extreme salt stress by 55 to 205% after nine rounds of microbiome selection. Although we artificially selected microbiomes under controlled greenhouse conditions that differ from outdoor conditions, increasing seed production by 55 to 205% under extreme salt stress is a remarkable enhancement of plant productivity compared to traditional plant breeding. We describe a series of additional experimental protocols that will advance insights into key parameters that determine efficacy and response to microbiome selection.

Age-dependent Radiation Dose Rates from Canine Sn-117m Treatments.

ABSTRACT: Tin-117 m (Sn-117m) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The decay process for Sn-117m is internal conversion wherein IC electrons and auger electrons provide the therapeutic effect. Additionally, the most prominent gamma emission is 158.6 keV. The effective dose rate received by a person interacting at close distances with a treated dog is needed to determine the person's total dose and thus regulatory compliance. Simple measurement of the dose rate at a given distance does not provide an accurate measurement of the effective dose to a person due to the non-uniform nature of the radiation field at close distances. MNCP models of the interactions of five ages of humans at three distances were created to determine the effective dose rates using the methodology from NRC Regulatory Guide 8.40. Ratios of the effective dose rate to the person to the measured dose rate at 1 m from the same source were calculated.

Corrigendum: Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic.

[This corrects the article DOI: 10.3389/fonc.2018.00652.].

Anxiolytic effects of NLRP3 inflammasome inhibition in a model of chronic sleep deprivation.

Sleep deprivation is a form of stress that provokes both inflammatory responses and neuropsychiatric disorders. Because persistent inflammation is implicated as a physiological process in anxiety disorders, we investigated the contributions of NLRP3 inflammasome signaling to anxiety and anxiolytic properties of flavanol diets in a model of chronic sleep deprivation. The results show a flavanol-rich dietary preparation (FDP) exhibits anxiolytic properties by attenuating markers of neuroimmune activation, which included IL-1ß upregulation, NLRP3 signaling, and microglia activation in the cortex and hippocampus of sleep-deprived mice. Production of IL-1ß and NLRP3 were critical for both anxiety phenotypes and microglia activation. Individual FDP metabolites potently inhibited IL-1ß production from microglia following stimulation with NLRP3-specific agonists, supporting anxiolytic properties of FDP observed in models of sleep deprivation involve inhibition of the NLRP3 inflammasome. The study further showed sleep deprivation alters the expression of the circadian gene Bmal1, which critically regulated NLRP3 expression and IL-1ß production.

Farfield coherent infrasound generation using an air-propane burner.

An invaluable tool in the characterization of any receiver, propagation path, or detection system is a source with known and repeatable signal characteristics. This article presents the theoretical development and engineering design of a coherent (nonexplosive, periodic with controlled duration) infrasound source in the sub-hertz to several hertz band. Design of a sound source within this band is a difficult engineering challenge. The simple source equation, which will govern any portable human-fabricated infrasound source due to the long wavelengths, shows this fundamental difficulty. As frequency decreases, volume displacement must increase by the squared inverse factor of frequency in order to maintain an equal pressure amplitude at equal range. For this reason, the authors evaluate using the high energy density available in gas combustion to periodically displace large volumes of air within the open atmosphere. Prototype testing has verified the capability of generating continuous signals at a fundamental frequency of 0.25 Hz in the farfield-ranges in which pressure and particle velocity can be considered in-phase-where the product of the acoustic wavenumber and range is near 4.7. The generation of frequency content throughout the 0.25-4.0 Hz band with a reasonable signal-to-noise ratio was also demonstrated.

Prophylactic effect of flavanol rich preparation metabolites in promoting resilience to a mouse model of social stress.

Major depressive disorder (MDD) is a leading cause of disability, and there is an urgent need for new therapeutics. Stress-mediated induction of pro-inflammation in the periphery contributes to depression-like behaviors both in humans and in experimental models. Inflammatory cytokine interleukin-6 (IL-6) has emerged as a potential therapeutic target. Our studies demonstrated that metabolism of flavanol rich cocoa preparation (FRP) led to the accumulation of select phenolic acids that may contribute to its anti-inflammatory activity. Using a repeated social defeat stress (RSDS) model of depression, we showed that oral administration of FRP attenuates susceptibility to RSDS-mediated depression, supporting the further development of FRP as a novel therapeutic for the treatment of stress disorders and anxiety in humans.

Rapid Evaluation of CRISPR Guides and Donors for Engineering Mice.

Although the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/ CRISPR associated protein 9 (Cas9) technique has dramatically lowered the cost and increased the speed of generating genetically engineered mice, success depends on using guide RNAs and donor DNAs which direct efficient knock-out (KO) or knock-in (KI). By Sanger sequencing DNA from blastocysts previously injected with the same CRISPR components intended to produce the engineered mice, one can test the effectiveness of different guide RNAs and donor DNAs. We describe in detail here a simple, rapid (three days), inexpensive protocol, for amplifying DNA from blastocysts to determine the results of CRISPR point mutation KIs. Using it, we show that (1) the rate of KI seen in blastocysts is similar to that seen in mice for a given guide RNA/donor DNA pair, (2) a donor complementary to the variable portion of a guide integrated in a more all-or-none fashion, (3) donor DNAs can be used simultaneously to integrate two different mutations into the same locus, and (4) by placing silent mutations about every 6 to 10 bp between the Cas9 cut site and the desired mutation(s), the desired mutation(s) can be incorporated into genomic DNA over 30 bp away from the cut at the same high efficiency as close to the cut.

Landscape genomics of an obligate mutualism: Concordant and discordant population structures between the leafcutter ant Atta texana and its two main fungal symbiont types.

To explore landscape genomics at the range limit of an obligate mutualism, we use genotyping-by-sequencing (ddRADseq) to quantify population structure and the effect of host-symbiont interactions between the northernmost fungus-farming leafcutter ant Atta texana and its two main types of cultivated fungus. Genome-wide differentiation between ants associated with either of the two fungal types is of the same order of magnitude as differentiation associated with temperature and precipitation across the ant's entire range, suggesting that specific ant-fungus genome-genome combinations may have been favoured by selection. For the ant hosts, we found a broad cline of genetic structure across the range, and a reduction of genetic diversity along the axis of range expansion towards the range margin. This population-genetic structure was concordant between the ants and one cultivar type (M-fungi, concordant clines) but discordant for the other cultivar type (T-fungi). Discordance in population-genetic structures between ant hosts and a fungal symbiont is surprising because the ant farmers codisperse with their vertically transmitted fungal symbionts. Discordance implies that (a) the fungi disperse also through between-nest horizontal transfer or other unknown mechanisms, and (b) genetic drift and gene flow can differ in magnitude between each partner and between different ant-fungus combinations. Together, these findings imply that variation in the strength of drift and gene flow experienced by each mutualistic partner affects adaptation to environmental stress at the range margin, and genome-genome interactions between host and symbiont influence adaptive genetic differentiation of the host during range evolution in this obligate mutualism.

The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids.

Dietary polyphenols promote memory in models of sleep deprivation (SD), stress, and neurodegeneration. The biological properties of dietary polyphenols greatly depend upon the bioavailability of their phenolic metabolites derivatives, which are modulated by gut microbiota. We recently demonstrated that supplementation with grape-derived bioactive dietary polyphenol preparation (BDPP) improves SD-induced cognitive impairment. This study examined the role of the gut microbiota in the ability of BDPP to prevent memory impairment in response to SD. C57BL6/J mice, treated with antibiotics mix (ABX) or BDPP or both, were sleep-deprived at the end of a fear conditioning training session and fear memory was assessed the next day. Gut microbiota composition was analyzed in fecal samples and BDPP-driven phenolic acid metabolites extraction was measured in plasma. We report that the beneficial effect of BDPP on memory in SD is attenuated by ABX-induced dysbiosis. We identified specific communities of fecal microbiota that are associated with the bioavailability of BDPP-derived phenolic acids, which in turn, are associated with memory promotion. These results suggest the gut microbiota composition significantly affects the bioavailability of phenolic acids that drive the dietary polyphenols' cognitive resilience property. Our findings provide a preclinical model with which to test the causal association of gut microbiota-polyphenols, with the ultimate goal of potential developing dietary polyphenols for the prevention/treatment of cognitive impairment.