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Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

ABSTRACT: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is?~?80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P?=?0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P???0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.

SUBMITTER: Staley C

PROVIDER: S-EPMC7907225 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

Staley Christopher C Halaweish Hossam H Graiziger Carolyn C Hamilton Matthew J MJ Kabage Amanda J AJ Galdys Alison L AL Vaughn Byron P BP Vantanasiri Kornpong K Suryanarayanan Raj R Sadowsky Michael J MJ Khoruts Alexander A

Scientific reports 20210225 1

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potent ...[more]

PMID: 33633264

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Project description:Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m(2) (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (-3 ± 11 mg/dL, -3 ± 9 mg/dL, and -28 ± 124 nmol/L, respectively) over 12 wk (0-12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0-12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 ?mol/L; HD-FDS: 1.2 ± 0.1 ?mol/L) vs. controls (LD-C: 2.1 ± 0.2 ?mol/L; HD-C: 2.3 ± 0.2 ?mol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion molecules. Thus, HD-FDS exerted greater effects in lowering serum total and LDL cholesterol and NMR-derived small LDL particles vs. LD-FDS in the 12-wk study. These findings warrant additional investigation in larger trials. This trial was registered at clinicaltrials.gov as NCT01883401.

Dataset Information

Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

Publications

Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

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