Background Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease. Objective We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability. Methods Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI). Results The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT. Conclusion FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.

Intestinal microbiota, diet, and physical activity are inextricably linked to inflammation occurring in the presence of tumor progression and declining neurocognition. This study aimed to explore how fecal microbiota, inflammatory biomarkers, and neurocognitive behavior are influenced by voluntary exercise and surplus dietary protein and folic acid which are common health choices. Dietary treatments provided over 8 weeks to C57BL/CJ male mice (N = 76) were: Folic Acid (FA) Protein (P) Control (FPC, 17.9% P; 2 mgFA/kg); Folic Acid Deficient (FAD); Folic Acid Supplemented (FAS; 8 mgFA/kg); Low Protein Diet (LPD, 6% P); and High Protein Diet (HPD, 48% P). FAS mice had decreased plasma HCys (p < 0.05), therefore confirming consumption of FA. Objectives included examining influence of exercise using Voluntary Wheel Running (VWR) upon fecal microbiota, inflammatory biomarkers C - reactive protein (CRP), Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), nuclear factor kappa ß subunit (NF-κßp65), Caspase-3 (CASP3), Tumor Necrosis Factor-alpha (TNF-α), and neurocognitive behavior. CRP remained stable, while a significant exercise and dietary effect was notable with decreased VEGF (p < 0.05) and increased CASP3 (p < 0.05) for exercised HPD mice. Consumption of FAS did significantly increase (p < 0.05) muscle TNF-α and the ability to build a nest (p < 0.05) was significantly decreased for both FAD and LPD exercised mice. Rearing behavior was significantly increased (p < 0.05) in mice fed HPD. An emerging pattern with increased dietary protein intake revealed more distance explored in Open Field Testing. At week 1, both weighted and unweighted UniFrac principal coordinates analysis yielded significant clustering (permanova, p ≤ 0.05) associated with the specific diets. Consumption of a HPD diet resulted in the most distinct fecal microbiota composition. At the phylum level–comparing week 1 to week 8–we report a general increase in the Firmicutes/Bacteroidetes ratio, characterized by an outgrowth of Firmicutes by week 8 in all groups except the HPD. MaAsLin2 analysis corroborates this finding and emphasizes an apparent inversion of the microbiome composition at week 8 after HPD. Explicit modification of oncogenic inflammatory biomarkers and fecal microbiome post high FA and protein intake along with voluntary exercise contributed to current underlying evidence that this diet and exercise relationship has broader effects on human health and disease–perhaps importantly as a practical modulation of cancer progression and declining neurocognition.

Our purpose was to investigate the utility of 18 F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18 F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18 F-FDG SUV mean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUV mean in left anterior descending segments (P 5 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P # 0.02). Further, a significant reduction in left ventricular stroke volume (27%) was seen (P , 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18 F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

Purpose: To investigate the utility of hybrid 18FDG-PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month post-radiation therapy (RT) in patients with left-sided breast cancer.Methods: Fifteen left-sided breast cancer patients enrolled in the RICT-BREAST study underwent hybrid PET/MRI cardiac imaging at baseline and one-month after standard RT. Eleven patients received deep-inspiration breath-hold RT, while others received free-breathing RT. A list-mode 18FDG/PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change of mean 18FDG standard uptake and analyzed based on the coronary vascular territory (left anterior descending (LAD), left circumflex or right coronary artery).MR assessments, including LV functional and extracellular volume matrices (ECV), were extracted from T1 (pre and during-constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during PET acquisition. Cardiac injury and inflammation biomarker measurements of hs-TnT, hs-CRP and erythrocyte sedimentation rate were compared at the 1-month follow-up in this study.Results: At one-month follow-up, a significant increase (10%) of 18FDG/PET myocardial uptake (meanSUVbw) in LAD segments (p=0.04) and ECV in slices at the apex (6%) and base (5%) were detected (p≤0.02). Further, a significant reduction of LV stroke volume (-7%) was seen (p <0.02). No significant changes in all circulating biomarkers at follow-up were shown. Conclusions: 18FDG/PET myocardial uptake and functional MR, including SV and ECV were sensitive to changes at one-month after breast cancer RT with findings suggesting an acute cardiac inflammatory response which is an important cardiotoxicity surrogate to RT. The clinical pilot study (NCT03748030, November 16, 2018) was approved by the Western University Human Research Ethics Board (HSREB ID 112991), funded by Lawson Strategic Research Fund (R19-292).