Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments DOI Creative Commons
Torben Sølbeck Rasmussen, Xiaotian Mao, Sarah Förster

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 17, 2023

ABSTRACT Background Fecal microbiota transplantation (FMT) and fecal virome (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) FMT or FVT hinders their wider clinical application less acute diseases. Methods To overcome these challenges, we developed methods to broaden FVT’s while maintaining efficacy increasing safety. Specifically, employed following approaches: 1) Chemostat-fermentation reproduce bacteriophage component remove viruses (FVT-ChP), 2) solvent-detergent treatment inactivate enveloped (FVT-SDT), 3) pyronin-Y inhibit RNA-virus replication (FVT-PyT). We assessed processed FVTs a C. infection mouse model compared them untreated (FVT-UnT), FMT, saline. Results FVT-SDT, FVT-UnT, FVT-ChP reduced incidence mice reaching humane endpoint (0/8, 2/7, 3/8, respectively) FVT-PyT, saline control (5/8, 7/8, 5/7, significantly load colonizing cells toxin A/B levels. There was potential elimination colonization, 7 out 8 treated FVT-SDT testing negative qPCR. In contrast, all other treatments exhibited continued presence . Moreover, results were supported by changes microbiome profiles, cecal cytokine levels histopathological findings. Assessment viral engraftment FMT/FVT host-phage correlations analysis suggested that phages likely an important contributing factor associated efficacy. Conclusions This proof-of-concept study show specific modifications hold promise addressing related variability risks. Two strategies lead limiting colonization mice, solvent/detergent chemostat-propagation emerging as promising approaches.

Language: Английский

The gut virome is associated with stress-induced changes in behaviour and immune responses in mice DOI Creative Commons
Nathaniel L. Ritz, Lorraine A. Draper, Thomaz F. S. Bastiaanssen

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 359 - 376

Published: Feb. 5, 2024

The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work focused primarily on of bacteriome. gut virome constitutes a major portion microbiome, with bacteriophages having potential remodel bacteriome structure and activity. Here we use mouse model chronic social stress, employ 16S rRNA whole metagenomic sequencing faecal pellets determine how is modulated by contributes effects stress. We found that led behavioural, immune alterations mice were associated changes bacteriophage class Caudoviricetes unassigned viral taxa. To whether these causally related stress-associated behavioural or physiological outcomes, conducted transplant from before autochthonously transferred it undergoing transfer protected against behaviour sequelae restored stress-induced select circulating cell populations, cytokine release, gene expression amygdala. These data provide evidence plays modulation during indicating populations should be considered when designing future microbiome-directed therapies.

Language: Английский

Citations

34
Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma DOI

Suki Ha,

Vincent Wai‐Sun Wong, Xiang Zhang

et al.

Gut, Journal Year: 2024, Volume and Issue: 74(1), P. 141 - 152

Published: June 29, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of injuries, ranging from hepatic steatosis, metabolic steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and gut microbial community. Host genetics influence composition microbiome, while microbiota their derived metabolites can induce epigenetic modifications affect development MASLD. The exploration intricate relationship microbiome genetic/epigenetic makeup is anticipated yield promising avenues for therapeutic interventions targeting MASLD its associated conditions. In this review, we summarise effects alterations in MASLD-HCC. We further discuss research findings demonstrating genetics/epigenetics, emphasising significance interconnection prevention treatment.

Language: Английский

Citations

21
Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments DOI Creative Commons
Torben Sølbeck Rasmussen, Xiaotian Mao, Sarah Förster

et al.

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: July 1, 2024

Abstract Background Fecal microbiota transplantation (FMT) and fecal virome (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) FMT or FVT hinder their wider clinical application less acute diseases. Methods To overcome these challenges, we developed methods to broaden FVT’s while maintaining efficacy increasing safety. Specifically, employed following approaches: (1) chemostat-fermentation reproduce bacteriophage component remove viruses (FVT-ChP), (2) solvent-detergent treatment inactivate enveloped (FVT-SDT), (3) pyronin-Y inhibit RNA virus replication (FVT-PyT). We assessed processed FVTs a C. infection mouse model compared them untreated (FVT-UnT), FMT, saline. Results FVT-SDT, FVT-UnT, FVT-ChP reduced incidence mice reaching humane endpoint (0/8, 2/7, 3/8, respectively) FVT-PyT, saline (5/8, 7/8, 5/7, significantly load colonizing cells associated toxin A/B levels. There was potential elimination colonization, seven out eight treated FVT-SDT testing negative qPCR. In contrast, all other treatments exhibited continued presence . Moreover, results were supported by changes microbiome profiles, cecal cytokine levels, histopathological findings. Assessment viral engraftment FMT/FVT host-phage correlations analysis suggested that phages likely an important contributing factor efficacy. Conclusions This proof-of-concept study shows specific modifications hold promise addressing related variability risks. Two strategies lead limiting colonization mice, solvent/detergent chemostat propagation emerging as promising approaches.

Language: Английский

Citations

10
The role of the early-life gut microbiome in childhood asthma DOI Creative Commons
Ulrika Boulund, Jonathan Thorsen, Urvish Trivedi

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 30, 2025

Asthma is a chronic disease affecting millions of children worldwide, and in severe cases requires hospitalization. The etiology asthma multifactorial, caused by both genetic environmental factors. In recent years, the role early-life gut microbiome relation to has become apparent, supported an increasing number population studies, vivo research, intervention trials. Numerous factors, which for decades have been associated with risk developing childhood asthma, are now being linked through alterations microbiome. These factors include cesarean birth, antibiotic use, breastfeeding, having siblings or pets, among others. Association studies highlighted several specific microbes that altered but these can vary between phenotype. This demonstrates importance microbial ecosystem necessity well-designed validate underlying mechanisms guide future clinical applications. this review, we examine current literature on identify research gaps allow microbial-focused therapeutic applications asthma.

Language: Английский

Citations

0
Reproducible chemostat cultures to eliminate eukaryotic viruses from fecal transplant material DOI Creative Commons
Signe Adamberg, Torben Sølbeck Rasmussen,

Sabina Brigitte Larsen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 15, 2023

ABSTRACT The effect of fecal microbiota transplantation (FMT) on various gut-related diseases is intensively investigated in clinical trials. In addition to bacteria, the gut microbiome also contains eukaryotic, archaeal, and bacterial viruses (bacteriophages, short phages), which collectively referred as virome. Application FMT settings associated with a potential risk for recipient transferring infectious eukaryotic or despite strict screening procedures donor material. A safer more targeted method modulate therefore needed extend application width FMT. Emerging evidence suggests that phages play key role maintaining balanced well efficacy. Thus, phageome from cultured may be efficient alternative bacteriome than Here, we analyzed dynamic changes viromes mice cecal human matter inoculated chemostat cultures. Sequencing results showed relative abundance remarkably decreased during continuous cultivation, likely due lack hosts. corresponding profiles dilution rate dependency, reproducibility between biological replicates, maintained high diversity although being different inoculum phageome. This proof-of-concept study constitute first step developing therapeutic tools target broad spectrum thereby replacing phage-mediated therapy.

Language: Английский

Citations

5
Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments DOI Creative Commons
Torben Sølbeck Rasmussen, Xiaotian Mao, Sarah Förster

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 17, 2023

ABSTRACT Background Fecal microbiota transplantation (FMT) and fecal virome (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) FMT or FVT hinders their wider clinical application less acute diseases. Methods To overcome these challenges, we developed methods to broaden FVT’s while maintaining efficacy increasing safety. Specifically, employed following approaches: 1) Chemostat-fermentation reproduce bacteriophage component remove viruses (FVT-ChP), 2) solvent-detergent treatment inactivate enveloped (FVT-SDT), 3) pyronin-Y inhibit RNA-virus replication (FVT-PyT). We assessed processed FVTs a C. infection mouse model compared them untreated (FVT-UnT), FMT, saline. Results FVT-SDT, FVT-UnT, FVT-ChP reduced incidence mice reaching humane endpoint (0/8, 2/7, 3/8, respectively) FVT-PyT, saline control (5/8, 7/8, 5/7, significantly load colonizing cells toxin A/B levels. There was potential elimination colonization, 7 out 8 treated FVT-SDT testing negative qPCR. In contrast, all other treatments exhibited continued presence . Moreover, results were supported by changes microbiome profiles, cecal cytokine levels histopathological findings. Assessment viral engraftment FMT/FVT host-phage correlations analysis suggested that phages likely an important contributing factor associated efficacy. Conclusions This proof-of-concept study show specific modifications hold promise addressing related variability risks. Two strategies lead limiting colonization mice, solvent/detergent chemostat-propagation emerging as promising approaches.

Language: Английский

Citations

4