Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh

EBioMedicine, Год журнала: 2016, Номер 4, С. 124 - 137

Опубликована: Янв. 5, 2016

Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of viruses infecting pathogen a species-specific way, potential alternative.T4-like coliphages or commercial Russian coliphage product placebo was orally given over 4 days to Bangladeshi children hospitalized with acute diarrhea. Safety oral phage assessed clinically and by functional tests; Escherichia coli titers enteropathogens were determined stool quantitative diarrhea parameters (stool output, frequency) measured. Stool microbiota studied 16S rRNA gene sequencing; genomes four fecal Streptococcus isolates sequenced.No adverse events attributable application observed (primary safety outcome). Fecal increased treated control children, but did not show substantial intestinal replication (secondary microbiology 60% suffered from microbiologically proven E. diarrhea; most frequent diagnosis ETEC infections. Bacterial co-pathogens also detected. Half patients contained phage-susceptible colonies stool. represented less than 5% bacteria. showed only short-lived peak otherwise close threshold for T4 vitro. An interim analysis after enrollment 120 no amelioration parameter PT standard care (tertiary clinical characterized an overgrowth belonging gallolyticus salivarius species groups, their abundance correlated outcome, genome sequencing identify virulence genes.Oral safe gut transit failed achieve amplification improve possibly due insufficient coverage too low requiring higher doses. More knowledge needed on vivo phage-bacterium interaction role childhood successful PT.The study supported grant Nestlé Nutrition Health Science. The trial registered Identifier NCT00937274 at ClinicalTrials.gov.

Язык: Английский

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Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians

Nature, Год журнала: 2021, Номер 599(7885), С. 458 - 464

Опубликована: Июль 29, 2021

Язык: Английский

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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Nature, Год журнала: 2020, Номер 581(7808), С. 310 - 315

Опубликована: Май 6, 2020

Язык: Английский

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Species–function relationships shape ecological properties of the human gut microbiome

Nature Microbiology, Год журнала: 2016, Номер 1(8)

Опубликована: Июнь 13, 2016

Язык: Английский

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Major microbiota dysbiosis in severe obesity: fate after bariatric surgery

Gut, Год журнала: 2018, Номер 68(1), С. 70 - 82

Опубликована: Июнь 13, 2018

Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation severe obesity. Bariatric surgery (BS) improves inflammation obesity is microbiota modifications. Here, we characterised obesity-associated dysbiosis (ie, MGR, composition functional characteristics) assessed whether BS would rescue these changes.Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects followed at 1, 3 12 months post-BS. Gut serum metabolome analysed using shotgun metagenomics liquid chromatography mass spectrometry (LC-MS). Confirmation groups included.Low (LGC) was present 75% of patients correlated increased trunk-fat comorbidities (type 2 diabetes, hypertension severity). Seventy-eight metagenomic species altered LGC, among which 50% body metabolic phenotypes. Nine metabolites (including glutarate, 3-methoxyphenylacetic acid L-histidine) modules containing protein families involved their strongly low MGR. MGR 1 year postsurgery, most RYGB remained post-BS, despite greater improvement than AGB patients.We identified major alterations include decreased related pathways linked deteriorations. The full post-BS calls additional strategies to improve the ecosystem microbiome-host interactions obesity.NCT01454232.

Язык: Английский

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