How’s your microbiota? Let’s check your urine.

Jenq, Robert R.

doi:10.1182/blood-2015-08-661504

Cited by 10 publications

(8 citation statements)

References 9 publications

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“…We saw similar taxa associated with high indole levels in stool samples (Figure 3 and Supplementary Figure 2). Bacilli were enriched in samples with low fecal indole levels, as was previously reported for low urinary 3-IS levels [39]. An analogous trend occurred in butyrate fecal levels; high butyrate levels were associated with groups of bacteria within the Clostridia class, and low butyrate levels were enriched for groups of bacteria within the Bacilli class.…”

Section: Discussionsupporting

confidence: 75%

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study

Galloway-Peña

Peterson

Farida

et al. 2019

Open Forum Infectious Diseases

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Background Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers. Methods Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry. Results Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03). Conclusions Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.

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Section: Discussionsupporting

confidence: 75%

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study

Galloway-Peña

Peterson

Farida

et al. 2019

Open Forum Infectious Diseases

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“…5D). The indole metabolite 3-indoxyl sulfate, an indirect measure of indole production by intestinal microbes (29,30), was readily detected in urine from animals colonized with K12, but appeared at significantly lower levels in animals colonized with K12ΔtnaA (Fig. 5E).…”

Section: Indole Limits Age-dependent Changes In Gene Expression Andmentioning

confidence: 99%

Indoles from commensal bacteria extend healthspan

Sonowal

Swimm

Sahoo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

154

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Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.C. elegans | aging | frailty | aryl hydrocarbon receptor | microbiota R ecent advances in health care have contributed to a significant increase in life expectancy of individuals, especially in developed countries, which predict an expansion of geriatric populations by as much as 350-fold over the next 40 y (1). However, extension of lifespan is often accompanied by increased frailty, and attendant increases in global healthcare expenditures are expected to be both massive and unsustainable (2). Such data highlight the need to develop means to extend healthspan, which is broadly defined as the length of time that an individual remains healthy and free of age-related infirmities (3, 4).Healthspan has often been convolved with lifespan, and extended healthspan has been associated with slowed onset of normal age-related changes (e.g., sarcopenia). Thus, mutations that extend lifespan might be expected to likewise extend healthspan. Recent studies in Caenorhabditis elegans indicate that, relative to wild-type animals, mutations that extend lifespan do indeed extend the period of youthfulness, in which animals are motile and resistant to bacterial infection (healthspan), but also extend the period of decrepitude or frailty, where animals are relatively immobile (5, 6) Other studies in C. elegans that take into account multiple measures of health, each normalized to maximal lifespan, indicate that mutations or conditions that extend lifespan minimally impact or ev...

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“…They found that mice exposed to lethal radiation as well as to chemotherapeutic conditioning regimens had lower urinary levels of 3-indoxyl sulfate (3-IS) [14]. This metabolite is derived from the tryptophan-derived indole, metabolized by the liver and excreted into the urine, known to be a potent endogenous agonist for the human aryl hydrocarbon receptor [54,55]. Mice colonized with an Escherichia coli strain unable to degrade tryptophan had lower 3-IS levels and lower post-transplant overall survival.…”

Section: Tryptophan-derived Ahr Ligandsmentioning

confidence: 99%

Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation

Masetti¹,

Zama²,

Leardini³

et al. 2021

IJMS

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The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.

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How’s your microbiota? Let’s check your urine.

Cited by 10 publications

References 9 publications

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study

Indoles from commensal bacteria extend healthspan

Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation

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