Gut Microbiota Metabolites, Amino Acid Metabolites, and Improvements in Diabetes-Related Traits—The POUNDS Lost Trial

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 297-OR
Author(s):  
YORIKO HEIANZA ◽  
DIANJIANYI SUN ◽  
GEORGE BRAY ◽  
LU QI
2021 ◽  
Vol 9 (12) ◽  
pp. 2430
Author(s):  
Eden Ephraim ◽  
Dennis E. Jewell

Age-related changes in the gut microbiota and metabolites are associated with the increased risk of detrimental conditions also seen with age. This study evaluated whether a test food with potential anti-aging benefits results in favorable changes in plasma and fecal metabolites and the fecal microbiota in senior cats. Forty healthy domestic cats aged 8.3–13.5 years were fed a washout food for 30 days, then control or test food for 30 days. After another 30-day washout, cats were switched to the other study food for 30 days. Assessment of plasma and fecal metabolites showed lower levels of metabolites associated with detrimental processes (e.g., uremic toxins) and higher levels of metabolites associated with beneficial processes (e.g., tocopherols) after cats consumed the test food compared with the control food. A shift toward proteolysis with the control food is supported by higher levels of amino acid metabolites and lower levels of carbohydrate metabolites. Operational taxonomic units of greater abundance with the test food positively correlated with carbohydrate and nicotinic acid metabolites, and negatively correlated with uremic toxins, amino acid metabolism, secondary bile salts, and branched-chain fatty acids. Taken together, the test food appears to result in greater levels of metabolites and microbiota associated with a healthier state.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 69-69 ◽  
Author(s):  
David Michonneau ◽  
Eleonora Latis ◽  
Laetitia Dubouchet ◽  
Regis Peffault De Latour ◽  
Marie Robin ◽  
...  

Abstract Introduction Many efforts have been attempted to improve our understanding of GVHD pathophysiology but few focused on human GVHD. Most studies have focused on the central role played by immune cells. However, recent researches have highlighted the influence of tissue microenvironment or of host microbiota in regulating allo-immune response. In human, circulating metabolites are produced by both tissues and gut microbiota. Among them, many biochemical compounds regulate immune cells function and could be the bridge between microbiota, tissues and the immune system. The aim of this study was to characterize metabolomics alterations associated with allo-HSCT and to determine biochemical pathway specifically involved during acute GVHD. Methods We collected donors and recipients' frozen plasma from a monocentric (n=43) and a multicentric cohort (n=56) of patients who underwent transplantation from an HLA-identical sibling in France. Donors' samples were collected before stem cell collection. Recipient's samples were obtained at acute GVHD onset or at day + 90 in patients without GVHD. After protein removal, plasma extracts were analyzed by two separate reverse phase (RP)/UPLC-MS/MS methods with positive ion mode electrospray ionization (ESI), one for analysis by RP/UPLC-MS/MS with negative ion mode ESI and one for analysis by HILIC/UPLC-MS/MS with negative ion mode ESI. Compounds were identified by comparison to library entries of purified standards or recurrent unknown entities. Peaks were quantified using area-under-the-curve. All statistical analyses were performed with R 3.5.0 and the MetaboAnalystR package. Results More than 800 circulating metabolites were identified in the 2 cohorts, belonging to lipid (43.6%), amino acid (22.2%), xenobiotics (19.1%), nucleotide (4.2%), carbohydrate (3.6%), cofactors and vitamins (3.4%), peptide (2.8%) and energy (1.1%) pathways. After allo-HSCT, the comparison of metabolomics profiles of recipients without GVHD with those of healthy related donors revealed major changes in 222 metabolites (with a significance threshold at p<0.05). SAM and Volcano Plot analysis (with a fold change (FC) > 2 and p<0.05) highlighted significant modification in 43 metabolites. In the absence of acute GvHD, allo-HSCT was mainly characterized by a higher level of primary bile acids, mono and diacylglycerol, but a decrease of phospholipid, sphingolipid and secondary bile acid metabolites. Interestingly, polyamine, including N-acetyl putrescine (FC=5.5, p<0.001) and N-acetyl spermidine (FC=3.7, p<0.0001), were increased, suggesting that these microbiota-derived metabolites might play a protective role on gut integrity in patients without GVHD. After comparison of recipients with or without GvHD, we were able to identify specific metabolomics changes associated with the onset of GvHD, irrespective of age, sex and feeding of patients. Acute GvHD was associated with a major decrease of plasmalogen and lysoplasmalogen (FC<0.5, p<0.0001), that may play a role in protection against oxidative stress induced by ROS. By contrast, medium and long chain fatty and polyunsaturated acid were strongly increased (FC>2, p<0.01). Most metabolites of amino acid pathways were decreased at onset of acute GvHD. Among them, Aryl Hydrocarbon receptor ligands were diminished in patients with GvHD, especially host- and microbiota-derived tryptophan metabolites such as 3-indoxyl sulfate (p=0.0001), indole acetate (p=0.03), indole propionate (p=0.03) and N-acetyl kynurenine (p=0.04). Many other gut microbiota-derived metabolites were significantly decreased in patients with GvHD, suggesting that major microbiota injury after allo-HSCT may regulate allo-immune responses through the production of metabolites with immunomodulatory properties. Discussion Our results demonstrate that allo-HSCT is associated with major metabolomics changes in recipients, which might me due to drug intakes, metabolic stress or microbiota alteration. GvHD was characterized by specific changes in complex lipid metabolism and amino acid metabolites that are involved in immune cells regulation and inflammation. This study highlights the potential role of circulating metabolites in GvHD pathophysiology that could be targeted for prophylaxis or treatment. Figure Figure. Disclosures Peffault De Latour: Pfizer Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S42-S42
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.


2017 ◽  
Vol 47 ◽  
pp. 15-15
Author(s):  
A Fox ◽  
M van Ampting ◽  
MO Nijhuis ◽  
H Wopereis ◽  
A Butt ◽  
...  

2020 ◽  
Vol 6 (1) ◽  
pp. eaax6208 ◽  
Author(s):  
Su-Ling Zeng ◽  
Shang-Zhen Li ◽  
Ping-Ting Xiao ◽  
Yuan-Yuan Cai ◽  
Chu Chu ◽  
...  

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.


2019 ◽  
Vol 484 (2) ◽  
pp. 238-242
Author(s):  
N. A. Semenova ◽  
P. E. Menshchikov ◽  
A. V. Manzhurtsev ◽  
M. V. Ublinskiy ◽  
T. A. Akhadov ◽  
...  

Intracellular concentrations of N acetyaspartate (NAA), aspartate (Asp) and glutamate (Glu) were determined for the first time in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and late post-traumatic period was investigated. In MRI‑negative frontal lobes one day after injury Asp and Glu levels were found to decrease by 45 and 35%, respectively, while NAA level decreased by only 16%. A negative correlation between NAA concentration and the ratio of Asp/Glu concentrations was found. In the long-term period, Glu level returned to normal, Asp level remained below normal by 60%, NAA level was reduced by 65% relative to normal, and Asp/Glu ratio significantly decreased. The obtained results revealed leading role of the neuronal aspartate-malate shuttle in violation of NAA synthesis.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhichang Wang ◽  
Jun Hu ◽  
Wenyong Zheng ◽  
Tao Yang ◽  
Xinkai Wang ◽  
...  

Abstract Background Early-weaning of piglets is often accompanied by severe disorders, especially diarrhea. The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host. Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets. However, the metabolic response to L. frumenti administration remains unclear. Then, we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L. frumenti or phosphate-buffered saline (PBS). Results A total of 100 6-day-old crossbred piglets (Landrace × Yorkshire) were randomly divided into two groups and piglets received PBS (sterile, 2 mL) or L. frumenti (suspension in PBS, 108 CFU/mL, 2 mL) by oral administration once per day from 6 to 20 days of age. Piglets were weaned at 21 days of age. Serum and liver samples for metabolomic analyses were collected at 26 days of age. Principal components analysis (PCA) showed that L. frumenti altered metabolism in serum and liver. Numerous correlations (P < 0.05) were identified among the serum and liver metabolites that were affected by L. frumenti. Concentrations of guanosine monophosphate (GMP), inosine monophosphate (IMP), and uric acid were higher in serum of L. frumenti administration piglets. Pathway analysis indicated that L. frumenti regulated fatty acid and amino acid metabolism in serum and liver. Concentrations of fatty acid β-oxidation related metabolites in serum (such as 3-hydroxybutyrylcarnitine, C4-OH) and liver (such as acetylcarnitine) were increased after L. frumenti administration. Conclusions Our findings suggest that L. frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets, where it promotes fatty acid β-oxidation and energy production. High serum concentrations of nucleotide intermediates, which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets, were further detected. These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vadim Osadchiy ◽  
Emeran A. Mayer ◽  
Kan Gao ◽  
Jennifer S. Labus ◽  
Bruce Naliboff ◽  
...  

Abstract Alterations in brain–gut–microbiome (BGM) interactions have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Here, we apply a systems biology approach, leveraging neuroimaging and fecal metabolite data, to characterize BGM interactions that are driving IBS pathophysiology. Fecal samples and resting state fMRI images were obtained from 138 female subjects (99 IBS, 39 healthy controls (HCs)). Partial least-squares discriminant analysis (PLS-DA) was conducted to explore group differences, and partial correlation analysis explored significantly changed metabolites and neuroimaging data. All correlational tests were performed controlling for age, body mass index, and diet; results are reported after FDR correction, with q < 0.05 as significant. Compared to HCs, IBS showed increased connectivity of the putamen with regions of the default mode and somatosensory networks. Metabolite pathways involved in nucleic acid and amino acid metabolism differentiated the two groups. Only a subset of metabolites, primarily amino acids, were associated with IBS-specific brain changes, including tryptophan, glutamate, and histidine. Histidine was the only metabolite positively associated with both IBS-specific alterations in brain connectivity. Our findings suggest a role for several amino acid metabolites in modulating brain function in IBS. These metabolites may alter brain connectivity directly, by crossing the blood–brain-barrier, or indirectly through peripheral mechanisms. This is the first study to integrate both neuroimaging and fecal metabolite data supporting the BGM model of IBS, building the foundation for future mechanistic studies on the influence of gut microbial metabolites on brain function in IBS.


2020 ◽  
Vol 11 (1) ◽  
pp. 472-482 ◽  
Author(s):  
Yuying Li ◽  
Peng Wang ◽  
Jie Yin ◽  
Shunshun Jin ◽  
Wenxuan Su ◽  
...  

d-Galactose induced chronic oxidative stress and also proved the positive effects of 0.5% ornithine α-ketoglutarate on altering the pig gut microbe, restoring serum amino acid and alleviating the growth-suppression induced by d-galactose chronic oxidative stress.


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