Breaking News
December 12, 2018 - Presence of antiphospholipid antibodies tied to first-time MI
December 12, 2018 - New study could help inform research on preventing falls
December 12, 2018 - Women and men with heart attack symptoms receive different care from EMS
December 12, 2018 - Disrupted biological clock can contribute to onset of diseases, USC study shows
December 12, 2018 - New publications generate controversy over the value of reducing salt consumption in populations
December 12, 2018 - New data from TAILORx trial confirms lack of chemo benefit regardless of race or ethnicity
December 12, 2018 - Specific class of biomarkers can accurately indicate the severity of cancer
December 12, 2018 - Meds Taken Do Not Vary With ADL Impairment in Heart Failure
December 12, 2018 - Long-term study shows that HIV-2 is deadlier than previously thought
December 12, 2018 - People living near oil and gas wells show early signs of cardiovascular disease
December 12, 2018 - IONTAS founder and pioneer in phage display technology attends Nobel Prize Award Ceremony
December 12, 2018 - People who eat red meat have high levels of chemical associated with heart disease, study finds
December 12, 2018 - New method uses water molecules to unlock neurons’ secrets
December 12, 2018 - New computer model predicts prostate cancer progression
December 12, 2018 - More Illnesses From Tainted Romaine Lettuce Reported
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - The EORTC Brain Tumor Group and Protagen AG collaborate to study immuno-competence of long-term glioblastoma survivors
December 12, 2018 - Insights into magnetotactic bacteria could guide development of biological nanorobots
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
December 12, 2018 - Researchers discover a ‘blind spot’ in atomic force microscopy
December 12, 2018 - Sprayable gel could help prevent recurrences of cancer after surgery
December 12, 2018 - SLU researchers explore how fetal exposure to inflammation can alter immunity in newborns
December 12, 2018 - How do patients want to discuss symptoms with clinicians?
December 12, 2018 - Zinc chelation may be able to deliver drug to insulin-producing cells
December 12, 2018 - Brigham researchers develop automated, low-cost tool to predict a woman’s ovulation
December 12, 2018 - Some people with Type 2 diabetes may be testing their blood sugar more often than needed
December 12, 2018 - Slow-growing type of glioma may be vulnerable to immunotherapy, suggests study
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Brazilian professors propose guidelines for therapeutic use of melatonin
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
December 11, 2018 - NICE releases new guidelines for diagnosis and management of COPD
December 11, 2018 - Without Obamacare penalty, think it’ll be nice to drop your plan? Better think twice
December 11, 2018 - Researchers capture high-resolution X-ray and NMR image of key immune regulator
December 11, 2018 - Natural flavonoid is effective at treating leishmanisis infections, study shows
December 11, 2018 - Avoidant grievers unconsciously monitor and block mind-wandering contents, study shows
December 11, 2018 - Study identifies how hantaviruses infect lung cells
December 11, 2018 - Improving PTSD care through genetics
December 11, 2018 - Dermatology providers show interest in recommending cannabinoids to patients
December 11, 2018 - Researchers to study effects of electroconvulsive therapy on Alzheimer’s patients with aggression
December 11, 2018 - Four dried fruits have lower glycemic index than starchy foods, study finds
December 11, 2018 - Optimization of drug dose sizes can reduce pharmaceutical wastage
December 11, 2018 - Ultrarestrictive opioid prescribing strategy linked with reduction in number of pills dispensed
December 11, 2018 - PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds
December 11, 2018 - Researchers aim to identify and target high blood pressure indicators
December 11, 2018 - Researchers identify immune cell subset that may drive chronic inflammation
December 11, 2018 - Ezogabine treatment reduces motor neuron excitability in ALS patients, study shows
December 11, 2018 - One implant, two prices. It depends on who’s paying.
December 11, 2018 - Standardizing feeding practices improves growth trends for micro-preemies
December 11, 2018 - COPD Tied to Obesity in Male, Female Never-Smokers
December 11, 2018 - Flossing: Information for Caregivers
December 11, 2018 - Does breastfeeding hormone protect against type 2 diabetes?
December 11, 2018 - Educating future doctors to prescribe physical activity for their patients
December 11, 2018 - Krystal 2000 microplate design improves fluorescence and luminescence measurement
December 11, 2018 - FDA clears mobile medical app to help increase retention in recovery program for opioid use disorder
December 11, 2018 - Overcoming Challenges in High-Speed Centrifugation Experiments
December 11, 2018 - Study shows link between neighborhoods’ socioeconomic status and dietary choices
December 11, 2018 - Lower BMI before obesity surgery predicts greater post-operative weight loss, study finds
December 11, 2018 - Obesity May Be Driving Rise in Uterine Cancers
D-serine produced by gut microbiota protects against acute kidney injury, show study

D-serine produced by gut microbiota protects against acute kidney injury, show study

image_pdfDownload PDFimage_print

Background

The kidney is an organ not only for excreting body waste by urine but also for maintaining body homeostasis in close cooperation with other organs. By producing various hormones, the kidney, for example, generates new erythrocytes in the bone marrow through erythropoietin, maintain bones turnover through activation of vitamin D, and controls blood pressure through renin-angiotensin system. In addition, it has recently been shown that the kidney plays an important role in affecting longevity. However, the relationship of the kidney to the gut (the gut microbiota1)) have not been studied in detail.

Amino acids exist as enantiomers, i.e., D-amino acids and their L-forms. The term “amino acids” has generally referred to the L-amino acid form or to the mixture of the L- and D- enantiomers. Recent progress in analytical technologies now makes it possible to distinguish the D-amino acids and their L-forms of about 20 amino acid species that are essential in our body. These amino acids are referred to as chiral amino acids. The D-amino acids and their L-forms of an amino acid have the same chemical formula, but are mirror images in three-dimensional structure, analogous to the difference between the left and right hand. Most interestingly, the D-amino acids and their L-forms differ significantly in their functions in living systems. L-amino acids are constituents of proteins, one of the most important components of living cells. On the other hand, the functions and mechanisms of production of D-amino acids are less clear.

Results

Researchers from Kanazawa University, in collaboration with those from Waseda University, RIKEN, Okayama University, Kyushu University and Kitasato University have investigated kidney functions in relation to the gut (the gut microbiota), paying particular attention to the fact that the kidney maintains body homeostasis and the internal environment in cooperation with a number of other organs.

To assess the effect of acute kidney injury (AKI)*2) on gut microbiota, we performed gut microbiota analysis with mouse feces after ischemia/reperfusion (I/R) injury to an AKI model. The gut microbiota were examined to reveal that specific gut bacteria were influenced by AKI. In addition, we explored the contribution of the gut microbiota to the pathogenesis of AKI. I/R injury was induced in germ-free (Gf) mice that have no gut microbiota with or without fecal transplantation from normal mice. I/R injury was worse in the Gf B6 mice than in the normal B6 mice. Interestingly, fecal transplantation from normal mice attenuated the renal pathology in the Gf B6 mice. These results suggested that the gut microbiota changed due to I/R injury and that possible substance(s) protective for the kidney was produced by the gut microbiota.

Next, in order to identify the substance(s) protecting the kidney against I/R injury produced by gut microbiota, comprehensive analyses of chiral amino acids were performed. While various D-amino acids were detected in the feces, only D-serine was detected in the kidney. The result suggested that D-serine was produced by the gut microbiota of AKI mice and transported to the kidney via the blood circulation. Furthermore, since D-serine was not detected in the feces of Gf mice, it was suggested that gut microbiota produced D-serine in response to AKI. In addition, D-serine metabolizing enzymes in the kidney were found to increase the D-serine concentration after I/R injury. Thus, the D-serine concentration in the kidney increased due to augmentation of D-serine production in the kidney in addition to the production of D-serine by the gut microbiota after I/R injury.

Further, in order to examine the effects of D-serine produced by the gut microbiota on the kidney, D-serine dissolved in drinking water was administered to normal mice. The oral administration of D-serine mitigated the kidney injury in normal mice and D-serine-depleted mice. These results showed that D-serine played roles in protecting the kidney from AKI.

Lastly, it was investigated whether similar mechanisms exist in human patients with AKI. The blood D-serine level of such patients was found to be higher than that of healthy subjects, showing a high correlation with creatinine, one of the markers of renal disorders.

Thus, it was revealed that some gut bacteria respond to AKI, producing D-serine, a substance protective for the kidney, thus affecting the kidney via the blood circulation.

Future prospects

This study has elucidated the mechanism by which the kidney interacts with gut microbiota through the D-amino acid. Further, genomic information concerning the gut microbiota that change upon AKI has been deposited in DDBJ/GenBank/EMBL from the present study. Information on the chiral amino acid analyses has also been published. These are expected to contribute to further studies on the kidney and the gut microbiota and to more studies of chiral amino acids.

In the future, it will be necessary to establish whether the change of D-amino acid levels due to AKI appear more rapidly than the biomarkers*3) known so far, and whether analogous mechanisms exist for chronic renal disorders.

We expect that the present study will contribute to the development of biomarkers and medications for AKI based on the utilization of D-amino acids.

Source:

Gut microbiota-derived D-serine protects against acute kidney injury

Tagged with:

About author

Related Articles