Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity.

ABSTRACT: Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effective ways to alleviate such complications remains to be explored. Here we show that 30% dietary restriction (DR) for 2 weeks dramatically increased the survival rate of 2-month-old female mice after lethal-dose MTX exposure. DR significantly reduced intestinal inflammation, preserved the number of basal crypt PCNA-positive cells, and protected the function of intestinal stem cells (ISCs) after MTX treatment. Furthermore, ablating intestinal microbiota by broad-spectrum antibiotics completely eliminated the protective effect achieved by DR. 16S rRNA gene deep-sequencing analysis revealed that short-term DR significantly increased the Lactobacillus genus, with Lactobacillus rhamnosus GG gavage partially mimicking the rescue effect of DR on the intestines of ad libitum fed mice exposed to lethal-dose MTX. Together, the current study reveals that DR could be a highly effective way to alleviate the lethal injury in the intestine after high-dose MTX treatment, which is functionally mediated by increasing the protective intestinal microbiota taxa in mice. Keywords: Dietary restriction, Methotrexate, Gut microbiota, Intestinal stem cells, intestinal toxicity.

SUBMITTER: Tang D

PROVIDER: S-EPMC7524152 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2.

Project description:Magnesium isoglycyrrhizinate (MgIG), which has been widely employed to treat chronic hepatitis, is synthesized from 18-β glycyrrhizic acid, a main component of traditional Chinese medicine Glycyrrhiza uralensis Fisch. Although the protective effects of MgIG on methotrexate (MTX)-induced liver toxicity have been well-documented, the underlying mechanism remains elusive. MTX was initially used to treat pediatric acute leukemia, and has been widely applied to psoriasis therapy. However, its clinical applications are limited due to hepatotoxicity and intestinal toxicity. Herein, prophylactic administration of MgIG (9 and 18 mg/kg/day) significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase in the serum of rats receiving intravenous injection of MTX (20 mg/kg body weight). MgIG also attenuated MTX-induced hepatic fibrosis. Moreover, it better protected against MTX-induced hepatocyte apoptosis and decreased the serum level of malondialdehyde than reduced glutathione (80 mg/kg/day) did. Interestingly, MTX-induced cyclooxygenase-2 (COX-2) expression, intestinal permeability and inflammation were attenuated after MgIG administration. In addition, MgIG (9 and 18 mg/kg) reduced MTX-induced colocalization of zonula occludens-1 (ZO-1) and connexin 43 (Cx43) in intestinal villi. In conclusion, MgIG exerted beneficial effects on MTX-induced hepatotoxicity and intestinal damage, as a potentially eligible drug for alleviating the hepatic and intestinal side effects of MTX during chemotherapy.

| S-EPMC6444054 | biostudies-literature

Dietary restriction increases variability in longevity.

Project description:Nutritional environments, particularly those experienced during early life, are hypothesized to affect longevity. A recent cross-taxa meta-analysis found that, depending upon circumstance, average longevity may be increased or decreased by early-life dietary restriction. Unstudied are the effects of diet during development on among-individual variance in longevity. Here, we address this issue using emerging methods for meta-analysis of variance. We found that, in general, standard deviation (s.d.) in longevity is around 8% higher under early-life dietary restriction than a standard diet. The effects became especially profound when dietary insults were experienced prenatally (s.d. increased by 29%) and/or extended into adulthood (s.d. increased by 36.6%). Early-life dietary restriction may generate variance in longevity as a result of increased variance in resource acquisition or allocation, but the mechanisms underlying these largely overlooked patterns clearly warrant elucidation.

| S-EPMC5377042 | biostudies-literature

Recurrent application of dietary restriction reduces tumor load and increases lifespan in an intestinal cancer model

Project description:Intestinal cancers are highly responsive to their nutrient environment. However, previous studies integrating nutrition into the network of cancer progression are largely inconsistent. We therefore investigated the effects of dietary restriction, which is the most consistently found beneficial nutritional intervention, on the development of intestinal stem cell tumors in a Drosophila melanogaster model. Submission to dietary restriction led to a decline in tumor mass and a morphological as well as functional rehabilitation of the intestine. Nevertheless, flies submitted to dietary restriction exhibited a drastically reduced lifespan due to substantial loss of body mass. To circumvent these destructive consequences, we applied a nutritional regimen consisting of alternating phases of dietary restriction and a fully nutritious diet. Strikingly, the recurrent diet reduced tumor mass and reinstated gut functionality to the same extend as continuous dietary restriction, while restoring the lifespan of tumor-bearing flies back to the level of healthy controls.

2021-07-05 | GSE134485 | GEO

Biochemical Mechanisms of Pathogen Restriction by Intestinal Bacteria.

Project description:The intestine is a highly complex ecosystem where many bacterial species interact with each other and host cells to influence animal physiology and susceptibility to pathogens. Genomic methods have provided a broad framework for understanding how alterations in microbial communities are associated with host physiology and infection, but the biochemical mechanisms of specific intestinal bacterial species are only emerging. In this review, we focus on recent studies that have characterized the biochemical mechanisms by which intestinal bacteria interact with other bacteria and host pathways to restrict pathogen infection. Understanding the biochemical mechanisms of intestinal microbiota function should provide new opportunities for therapeutic development towards a variety of infectious diseases.

| S-EPMC6038137 | biostudies-literature

Necroptosis increases with age and is reduced by dietary restriction.

Project description:Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7- and 1.9-fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P-MLKL and P-RIPK3 to levels similar to adult mice. An increase in the expression of RIPK1 (1.6-fold) and MLKL (2.7-fold), not RIPK3, was also observed in eWAT of old mice, which was reduced by DR in old mice. The increase in necroptosis was paralleled by an increase in 14 inflammatory cytokines, including the pro-inflammatory cytokines IL-6 (3.9-fold), TNF-? (4.7-fold), and IL-1? (5.1-fold)], and 11 chemokines in old mice. DR attenuated the expression of IL-6, TNF-?, and IL-1? as well as 85% of the other cytokines/chemokines induced with age. In contrast, inguinal WAT (iWAT), which is less inflammatory, did not show any significant increase with age in the levels of P-MLKL and MLKL or inflammatory cytokines/chemokines. Because the changes in biomarkers of necroptosis in eWAT with age and DR paralleled the changes in the expression of pro-inflammatory cytokines, our data support the possibility that necroptosis might play a role in increased chronic inflammation observed with age.

| S-EPMC6052392 | biostudies-literature

Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.

Project description:Commensal intestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensal microbes remain poorly defined. Here, we show that commensal fungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenza A virus infection occurring upon commensal bacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae. The protective benefits of commensal fungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensal bacteria. Thus, commensal enteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria.

| S-EPMC5730478 | biostudies-literature

Dietary fat restriction increases fat taste sensitivity in people with obesity.

Project description:Individuals with obesity may be less sensitive to the taste of fat, and it is hypothesized that this is due to excess dietary fat intake. This study assessed the effect of a 6-week low-fat (LF) or portion control (PC) diet matched for weight loss on fat taste thresholds, fat perception, and preference in people with overweight/obesity.Participants (n = 53) completed a randomized dietary intervention and consumed either a LF diet (25% fat) or PC diet (33% fat) for 6 weeks. Fat taste thresholds (lowest detectable fat concentration), fat perception (discrimination ability), preference, and anthropometry were assessed at baseline and week 6.Consumption of a LF diet (n = 26) and PC diet (n = 27) reduced participants' weight (P < 0.001), with no significant differences between groups (LF, -2.9%, PC, -2.7%). Both diets resulted in a decrease in fat taste thresholds (P = 0.014), and the effect tended to be stronger in the LF diet vs. the PC diet (P = 0.060). The ability to perceive different fat concentrations in foods was increased after the LF diet only (P = 0.017); however, food preference did not change on either diet.A PC and LF diet both increase fat taste sensitivity in people with overweight/obesity, with the strongest effect after the LF diet.

| S-EPMC4745027 | biostudies-other

Translatome profiling of Drosophila intestinal enterocytes upon Dietary Restriction

Project description:We determined the actively translated mRNA induced/repressed by a Dietary Restriction intervention specifically in the differentiated enterocytes of the intestine. For this, we did a "genetic dissection" by expressing a tagged ribosomal subunit (RpL13A-His6FLAG) under the control of the tissue specific Myo1A-GAL4 driver, targetting its expression exclusively to the intestinal enterocytes. By performing a anti-flag pulldown we are then able to enrich our mRNA pool for transcripts that are directly bound to ribosomes and being actively translated. In this manner, we become one step closer to protein synthesis while profiling gene expression.

2016-09-16 | GSE76396 | GEO

Evolution under dietary restriction increases male reproductive performance without survival cost.

Project description:Dietary restriction (DR), a reduction in nutrient intake without malnutrition, is the most reproducible way to extend lifespan in a wide range of organisms across the tree of life, yet the evolutionary underpinnings of the DR effect on lifespan are still widely debated. The leading theory suggests that this effect is adaptive and results from reallocation of resources from reproduction to somatic maintenance, in order to survive periods of famine in nature. However, such response would cease to be adaptive when DR is chronic and animals are selected to allocate more resources to reproduction. Nevertheless, chronic DR can also increase the strength of selection resulting in the evolution of more robust genotypes. We evolved Drosophila melanogaster fruit flies on 'DR', 'standard' and 'high' adult diets in replicate populations with overlapping generations. After approximately 25 generations of experimental evolution, male 'DR' flies had higher fitness than males from 'standard' and 'high' populations. Strikingly, this increase in reproductive success did not come at a cost to survival. Our results suggest that sustained DR selects for more robust male genotypes that are overall better in converting resources into energy, which they allocate mostly to reproduction.

| S-EPMC4810831 | biostudies-literature

Sex-Specific Effects of Dietary Methionine Restriction on the Intestinal Microbiome.

Project description:Dietary methionine restriction is associated with improved health outcomes and an increase in lifespan in animal models. We have previously shown that an increase in dietary methionine induces alteration in the intestinal microbiome. The composition of the intestinal microbiota is a determinant of health and we, therefore, hypothesized that dietary methionine restriction would also induce changes in the murine microbiome. After one month on a methionine-restricted diet, five-month-old male and female C57BL/6 mice had decreased levels of serum methionine, without changes in body weight. We identified a decrease in the hepatic methylation status of animals fed a methionine-restricted diet compared to controls. This decrease was not associated with changes in DNA or protein methylation in the liver. In males, we saw an increase in families Bacteroidaceae and Verrucoccaceae (mostly A. mucinophila) and a decrease in Rumminococcaceae in animals fed a methionine-restricted diet compared to controls. In females, Bacteroidales family S24-7 was increased two-fold, while families Bacteroidaceae, Verrucoccaceae, Rumminococcaceae, and Rikenellaceae were decreased compared to controls. In summary, feeding a methionine-restricted diet for one month was associated with significant and sex-specific changes in the intestinal microbiome.

| S-EPMC7146121 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data