Breaking News
December 19, 2018 - World-first coeliac disease vaccine enters Phase 2 trials
December 19, 2018 - RNA sequencing offers novel insights into the microbiome
December 19, 2018 - A promising, effective vaccine for common respiratory disease
December 19, 2018 - Protein may slow progression of emphysema, study finds
December 19, 2018 - Studying atrial fibrillation — and exploring new frontiers in precision health
December 19, 2018 - A New Way To Get College Students Through A Psychiatric Crisis — And Back To School
December 19, 2018 - Optum, UnitedHealthcare take action to help people affected by North Carolina winter storms
December 18, 2018 - Weight change in middle-aged, elderly Chinese Singaporeans related to increased risk of death
December 18, 2018 - Immune cells sacrifice themselves to protect us from invading bacteria
December 18, 2018 - Watching brain cells fire, with a twist of gravitational waves
December 18, 2018 - 2018 in Review
December 18, 2018 - Getting the Most Out of the CLARITY Technique
December 18, 2018 - NVF shoes provide a viable option for track and road racing
December 18, 2018 - CRISPR may restore effectiveness of chemotherapies used to treat lung cancer
December 18, 2018 - New app accurately measures and charts progression of skin wounds
December 18, 2018 - Persistent Discrimination ID’d Among Physician Mothers
December 18, 2018 - Cellphone technology developed to detect HIV
December 18, 2018 - A Stanford doctor hits the field with the 49ers — as their airway management physician
December 18, 2018 - The Rise of Anxiety Baking
December 18, 2018 - Just one night of sleep deprivation increases the urge to eat
December 18, 2018 - Study reveals mechanism behind failed remyelination in MS
December 18, 2018 - New genetic testing method increases the precision of biomarker analysis
December 18, 2018 - Simple technique to effectively treat underdiagnosed cause of debilitating chest pain
December 18, 2018 - Barbershop-based medical intervention can successfully lower blood pressure, new data shows
December 18, 2018 - Food labels have caused changes in consumers’ intake and industry’s use of key additives
December 18, 2018 - Sickest children could benefit from split liver transplants
December 18, 2018 - Scientists create patient-specific model to identify most effective treatment for appendix cancer
December 18, 2018 - ‘Little Foot’ endocast reveals a small brain combining ape-like and human-like features
December 18, 2018 - New therapy for childhood blindness shows ‘very promising’ results
December 18, 2018 - Researchers discover promising new compound against Buruli ulcer
December 18, 2018 - Study finds significant use of traditional, complementary and alternative medicines in Sub-Saharan Africa
December 18, 2018 - California Farm Implicated in Outbreak of E. coli Tied to Romaine Lettuce
December 18, 2018 - Mobile health has power to transform HIV/AIDS nursing
December 18, 2018 - Celiac Vaccine in Clinical Trials at Columbia
December 18, 2018 - Research into mental health first aid prompts practical guidance and resources for workplace
December 18, 2018 - Researcher conducts study to investigate peripheral blood markers of Alzheimer’s disease
December 18, 2018 - Researchers identify link between mucus in the small airways and pulmonary fibrosis
December 18, 2018 - EU Commission’s Health Policy Platform to host EKHA program on transplantation
December 18, 2018 - Survivors of childhood Hodgkin lymphoma have high risk of developing solid tumors
December 18, 2018 - Small changes to cafeteria design can get kids to eat healthier, new assessment tool finds
December 18, 2018 - From Machines to Cyclic Compounds
December 18, 2018 - New study reveals best assessment tools to establish delirium severity
December 18, 2018 - Rice University scientists develop synthetic protein switches to control electron flow
December 18, 2018 - Home-based pulmonary function monitoring for teens with Duchenne muscular dystrophy
December 18, 2018 - Researchers identify potential target for new breast cancer treatments
December 18, 2018 - National Biofilms Innovation Centre award grant to Neem Biotech for novel anti-biofilm drug development
December 18, 2018 - Artificial intelligence and the future of medicine
December 18, 2018 - Montana State doctoral student receives grant for her work to improve neuroscience tool
December 18, 2018 - Early postpartum initiation of opioids associated with persistent use
December 18, 2018 - Russian scientists identify molecular ‘switch’ that could be target for treatment of allergic asthma
December 18, 2018 - Surgeons make more mistakes in the operating room during stressful moments, shows study
December 18, 2018 - Immune cells explode themselves to inform about the danger of invading bacteria
December 18, 2018 - Malnutrition in children with Crohn’s disease linked with increased risk of surgical complications
December 18, 2018 - FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC)
December 18, 2018 - The long and short of CDK12
December 18, 2018 - Hologic’s Cynosure division introduces TempSure Surgical RF technology in North America
December 18, 2018 - CMR Surgical partners with Nicholson Center to launch U.S.-based training program for Versius
December 18, 2018 - Findings reinforce guidelines for cautious use of antipsychotics in younger populations
December 18, 2018 - Study finds new strains of hepatitis C virus in sub-Saharan Africa
December 18, 2018 - New battery-free, implantable device aids weight loss
December 18, 2018 - Parental alcohol use disorder associated with offspring marital outcomes
December 18, 2018 - Novel Breast Imaging Technique Might Cut Unnecessary Biopsies
December 18, 2018 - What can a snowflake teach us about how cancer spreads in the body?
December 18, 2018 - Management of nausea and vomiting in pregnancy costs the NHS more than previously thought
December 18, 2018 - Green leafy vegetables may reduce risk of developing liver steatosis
December 18, 2018 - Veganism linked to nutrient deficiencies and malnutrition if not planned correctly
December 18, 2018 - Coming Soon: A Tiny Robot You Swallow to Help You Stay Healthy
December 18, 2018 - Modified malaria drug proven effective at inhibiting Ebola
December 18, 2018 - Study finds epigenetic differences in the brains of individuals with schizophrenia
December 18, 2018 - Fitness instructors’ motivational comments influence women’s body satisfaction
December 18, 2018 - Study focuses on modification of lipid nanoparticles for successful brain cell targeting
December 18, 2018 - New gut bacteria may be effective against obesity, metabolic and mental disorders
December 18, 2018 - New two-in-one powder aerosol to upgrade fight against deadly superbugs in lungs
December 18, 2018 - Biofilms feed with swirling flows
December 17, 2018 - Study identifies specific neurological changes related to traumatic brain injury
December 17, 2018 - New study confirms geographic bias in lung allocation for transplant
December 17, 2018 - Research focuses on optimization of solid lipid nanoparticle that encapsulates Vinorelbine bitartrate
December 17, 2018 - Carpal tunnel syndrome – Genetics Home Reference
December 17, 2018 - A novel insulin accelerant
December 17, 2018 - Tips for caring for patients with disabilities, from a mother and physician
Gut microbiota-derived D-serine protects against acute kidney injury

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

image_pdfDownload PDFimage_print
Comparison of the abundance of several species between the I/R-injured and the sham-operated mice at pre-I/R and days 2 and 10. Credit: Kanazawa University

Gut microbiota-derived metabolites play important roles in health and disease. In this study, we show the pathophysiological role of D-serine in association with the gut microbiota in humans and mice with acute kidney injury. The results demonstrate the renoprotective effects of D-serine derived from the gut microbiota; shed light on the interactions between the gut microbiota and the kidney; and highlight D-serine as a potential new therapeutic target and biomarker for acute kidney injury.

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 the 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 microbiota) has 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.

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.

(a) Although some free D-amino acids were detected in the feces of B6 mice with or without I/R, only D-serine can be detected in the kidney. (b) Free D-serine is increased in the feces, plasma, kidney, and urine after the I/R. Credit: Kanazawa University

To assess the effect of acute kidney injury (AKI)) 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 (Fig. 1). 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 (Fig. 2a). The result suggested that D-serine was produced by the gut microbiota of AKI mice and transported to the kidney via the blood circulation (Fig. 2b). 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.

Proposed model of the relationship between gut-derived D-serine and the kidney based on the results of this study. Credit: Kanazawa University

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 (Fig. 3).

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) known so far, and whether analogous mechanisms exist for chronic renal disorders.

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


Explore further:
Gut microbiota of mouse pups regulated by hydrogen peroxide produced through lactation

More information:
Yusuke Nakade et al, Gut microbiota–derived D-serine protects against acute kidney injury, JCI Insight (2018). DOI: 10.1172/jci.insight.97957

Provided by:
Kanazawa University

Tagged with:

About author

Related Articles