New Approaches to Microbiome-Based Therapies

Wong, Andrea C.; Levy, Maayan

doi:10.1128/msystems.00122-19

Cited by 98 publications

(64 citation statements)

References 21 publications

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“…From a clinical standpoint, our findings strengthen the difference between the use of a simple decolonization strategy based on the administration of oral antibiotics and a complex strategy based on probiotic supplementation, which takes into account the interaction between the probiotic itself, the gut resident flora, and the host's immune and intestinal cell. Therefore, the results of the present investigation may represent the starting point for future studies investigating the role of the probiotic for gut MDR microorganism decolonization [26,27].…”

Section: Discussionmentioning

confidence: 88%

Antibacterial Effectiveness of Fecal Water and In Vitro Activity of a Multi-Strain Probiotic Formulation against Multi-Drug Resistant Microorganisms

Oliva

et al. 2020

Microorganisms

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Introduction: Intestinal colonization with multi-drug resistant (MDR) microorganisms is a consequence of antimicrobial-induced gut dysbiosis. Given the effect of probiotics in modulating gut microbiota, the aim of the study was to investigate whether the ingestion of high concentration multi-strain probiotic formulation would change the antibacterial activity of the feces against clinical strains of MDR microorganisms. The corresponding in vitro antibacterial activity was also investigated. Materials/Methods: The feces of healthy donors (n = 6) were analyzed before and after a 7-day dietary supplementation with a multi-strain probiotic formulation and tested against MDR microorganisms of clinical concern (carbapenem-resistant (CR), Klebsiella pneumoniae (CR-Kp), CR-Acinetobacter baumannii (CR-Ab), CR-Pseudomonas aeruginosa (CR-Pa), and methicillin-resistant Staphylococcus aureus (MRSA)). The tested MDR pathogens were cultured with decreasing concentrations of fecal water obtained before and after the treatment period. Furthermore, to corroborate the results obtained from the feces of healthy donors, the in vitro antibacterial activity of probiotic formulation (both whole probiotic (WP) and probiotic surnatant (PS)) against the same collection of MDR microorganisms was evaluated at different incubation times throughout the minimum bactericidal dilution and the corresponding serial silution number. Results: While before probiotic administration, the fecal water samples did not inhibit MDR microorganism growth, after supplementation, a reduced bacterial growth was shown. Accordingly, a noticeable in vitro activity of WP and PS was observed. Conclusions: Although preliminary, these experiments demonstrated that a specific multi-strain probiotic formulation exhibits in vitro antibacterial activity against MDR microorganisms of clinical concern. If confirmed, these results may justify the administration of probiotics as a decolonization strategy against MDR microorganisms.

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Section: Discussionmentioning

confidence: 88%

Antibacterial Effectiveness of Fecal Water and In Vitro Activity of a Multi-Strain Probiotic Formulation against Multi-Drug Resistant Microorganisms

Oliva

et al. 2020

Microorganisms

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“…Recent advances in our understanding of the microbiome-immunity axis has spurred interest in how gut microbiota and their metabolic products, especially short chain fatty acids, can contribute to health outcomes and potentially be used for clinical purposes (3,(68)(69)(70)(71)(72)(73)(74). In order to fully appreciate the mechanisms by which gut metabolites like butyrate exert their immunomodulatory effects, it is necessary to understand how butyrate directly influences immune programs that contribute to infection and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Short chain fatty acid butyrate promotes virus infection by repressing interferon stimulated genes

Chemudupati

Smith

Fillinger

et al. 2020

Preprint

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Butyrate is an abundant metabolite produced by the gut microbiota and is known to modulate multiple immune system pathways and inflammatory diseases. However, studies of its effects on virus infection of cells are limited and enigmatic. We found that butyrate increases cellular infection and virus replication in influenza virus, reovirus, and human immunodeficiency virus infections. Further exploring this phenomenon, we found that addition of butyrate to cells deficient in type I interferon (IFN) signaling did not increase susceptibility to virus infection. Accordingly, we discovered that butyrate suppressed levels of specific IFN stimulated gene (ISG) products in human and mouse cells. Butyrate did not inhibit IFN-induced phosphorylation of transcription factors STAT1 and STAT2 or their translocation to the nucleus, indicating that IFN signaling was not disrupted. Rather, our data are suggestive of a role for inhibition of histone deacetylase activity by butyrate in limiting ISG induction. Global transcript analysis revealed that butyrate increases expression of more than 800 cellular genes, but represses IFN-induced expression of 60% of ISGs. Overall, we identify a new mechanism by which butyrate promotes virus infection via repression of ISGs. Our findings also add to the growing body of evidence showing that individual ISGs respond differently to type I IFN induction depending on the cellular environment, including the presence of butyrate. ImportanceButyrate is a lipid produced by intestinal bacteria that can regulate inflammation throughout the body. Here we show for the first time that butyrate influences the innate antiviral immune response mediated by type I IFNs. A majority of antiviral genes induced

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“…Gut microbiota have emerged as an attractive therapeutic target to promote healthy aging and anti-aging effects, which may result in improved quality of life [ 59 ]. The gut microbiota responds to dietary interventions very quickly, and short-term changes in the diet can alter the overall structure of the gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omic Analysis Reveals Different Effects of Sulforaphane on the Microbiome and Metabolome in Old Compared to Young Mice

et al. 2020

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Dietary factors modulate interactions between the microbiome, metabolome, and immune system. Sulforaphane (SFN) exerts effects on aging, cancer prevention and reducing insulin resistance. This study investigated effects of SFN on the gut microbiome and metabolome in old mouse model compared with young mice. Young (6–8 weeks) and old (21–22 months) male C57BL/6J mice were provided regular rodent chow ± SFN for 2 months. We collected fecal samples before and after SFN administration and profiled the microbiome and metabolome. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the gut microbiome, and metabolome. The SFN diet restored the gut microbiome in old mice to mimic that in young mice, enriching bacteria known to be associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. The tricarboxylic acid cycle decreased and amino acid metabolism-related pathways increased. Integration of multi-omic datasets revealed SFN diet-induced metabolite biomarkers in old mice associated principally with the genera, Oscillospira, Ruminococcus, and Allobaculum. Collectively, our results support a hypothesis that SFN diet exerts anti-aging effects in part by influencing the gut microbiome and metabolome. Modulating the gut microbiome by SFN may have the potential to promote healthier aging.

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New Approaches to Microbiome-Based Therapies

Cited by 98 publications

References 21 publications

Antibacterial Effectiveness of Fecal Water and In Vitro Activity of a Multi-Strain Probiotic Formulation against Multi-Drug Resistant Microorganisms

Antibacterial Effectiveness of Fecal Water and In Vitro Activity of a Multi-Strain Probiotic Formulation against Multi-Drug Resistant Microorganisms

Short chain fatty acid butyrate promotes virus infection by repressing interferon stimulated genes

Multi-Omic Analysis Reveals Different Effects of Sulforaphane on the Microbiome and Metabolome in Old Compared to Young Mice

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