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

Nakade, Yusuke; Iwata, Yasunori; Furuichi, Kengo; Mita, Masashi; Hamase, Kenji; Konno, Ryuichi; Miyake, Taito; Sakai, Norihiko; Kitajima, Shinji; Toyama, Tadashi; Shinozaki, Yukiko; Sagara, Akihiro; Miyagawa, Taro; Hara, Akinori; Shimizu, Miho; Kamikawa, Yasutaka; Sato, Kouichi; Oda, Megumi; Yoneda‐Nakagawa, Shiori; Yamamura, Yuta; Kaneko, Shuichi; Miyamoto, Tomofumi; Katane, Masumi; Homma, Hiroshi; Morita, Hidetoshi; Suda, Wataru; Hattori, Masahira; Wada, Takashi

doi:10.1172/jci.insight.97957

Cited by 109 publications

(110 citation statements)

References 41 publications

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“…For example, the oral administration of d-Asp increases its levels as identified in mice brains and enhances synaptic plasticity [45], consequently improving memory [46,47]. The d-amino acids produced by enterobacteria mitigate nephropathy in mice [48], and of the various d-amino acids made by enterobacteria, d-Ser has an especially high mitigative effect. When mice with nephropathy were dosed with d-Ser, the d-Ser dose mitigated the nephropathy of the mice, as expected.…”

Section: D-amino Acids In Fermentative Foodsmentioning

confidence: 99%

d-Amino Acids and Lactic Acid Bacteria

Kobayashi

2019

Microorganisms

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Proteins are composed of l-amino acids except for glycine, which bears no asymmetric carbon atom. Accordingly, researchers have studied the function and metabolism of l-amino acids in living organisms but have paid less attention to the presence and roles of their d-enantiomers. However, with the recent developments in analytical techniques, the presence of various d-amino acids in the cells of various organisms and the importance of their roles have been revealed. For example, d-serine (d-Ser) and d-aspartate (d-Asp) act as neurotransmitters and hormone-like substances, respectively, in humans, whereas some kinds of d-amino acids act as a biofilm disassembly factor in bacteria. Interestingly, lactic acid bacteria produce various kinds of d-amino acids during fermentation, and many d-amino acids taste sweet, compared with the corresponding l-enantiomers. The influence of d-amino acids on human health and beauty has been reported in recent years. These facts suggest that the d-amino acids produced by lactic acid bacteria are important in terms of the taste and function of lactic-acid-fermented foods. Against this background, unique d-amino-acid-metabolizing enzymes have been searched for and observed in lactic acid bacteria. This review summarizes and introduces the importance of various d-amino acids in this regard.Proteins are basically made up of 20 kinds of α-amino acids in the form of monomers, and these amino acids have at least one asymmetric carbon, except for glycine. This yields 19 kinds of amino acid (glycine has been excepted) with l-and d-form varieties. As proteins are made up of l-amino acids, many researchers, in fields such as medical, food, and nutritional science, have paid close attention to l-amino acids, giving rise to considerable knowledge of l-amino acids, including proteins. Until the 1970s, many researchers thought that d-amino acids were rare in nature and did not play an important role in living organisms. After that, however, d-alanine (d-Ala), d-glutamate (d-Glu), and d-aspartate (d-Asp) were found in bacterial cell walls as constituents, and d-amino acids were observed to exist in nature. This finding led to the conclusion that d-amino acids were only rarely present in bacterial cell walls, but in the 1990s, the development of analytical techniques, such as chiral column chromatography, meant that various kinds of d-amino acids were identified in free forms in diverse organisms. These d-amino acids were initially considered to be derived from foods or enterobacteria, but it is now known that some parts of d-amino acids such as d-serine (d-Ser) and d-Asp can be synthesized in mammalian cells. d-Amino acids have similar physical and chemical characteristics with l-amino acids, but the physiological functions of d-amino acids are completely different with those of l-amino acids. For example, d-Ser works as neurotransmitter in the brain, but l-Ser has no such role. Furthermore, d-amino acids are uncommon in living organisms, compared with l-amino acids, and despite the fact that some d-...

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Section: D-amino Acids In Fermentative Foodsmentioning

confidence: 99%

d-Amino Acids and Lactic Acid Bacteria

Kobayashi

2019

Microorganisms

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“…Another study suggested the potential protective effects of d-serine [45]. Although protective effects have not been demonstrated using the conventional kidney marker, creatinine, d-serine was reported to suppress kidney tubular damage according to the histological assessment of a rodent acute kidney injury model (ischemia/reperfusion model).…”

Section: Physiological Function Of D-serine In Kidneymentioning

confidence: 99%

d-Amino acids and kidney diseases

2020

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d-Amino acids are the recently detected enantiomers of l-amino acids. Accumulating evidence points their potential in solving the long-standing critical problems associated with the management of both chronic and acute kidney diseases. This includes estimating kidney function, early diagnosis and prognosis of chronic kidney disease, and disease monitoring. Among the d-amino acids, d-serine levels in the blood are strongly correlated with the glomerular filtration rate and are useful for estimating the function of the kidney. Urinary d-serine also reflects other conditions. The kidney proximal tubule reabsorbs serine with chiral-selectivity, with d-serine being reabsorbed much less efficiently than l-serine, and urinary excretion of d-serine is sensitive to the presence of kidney diseases. Therefore, assessing the intra-body dynamics of d-serine by measuring its level in blood and urinary excretion can be used to detect kidney diseases and assess pathophysiology. This new concept, the intra-body dynamics of d-serine, can be useful in the comprehensive management of kidney disease.

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“…In contrary, depletion of mouse gut microbiota by an antibiotic-cocktail significantly attenuates I/R-induced AKI associated with low expression of F4/80 macrophages and pro-inflammatory chemokines [ 89 ]. Intestinal microbiota modulates immune reactions in AKI through their metabolites such as short chain fatty acids, trimethylamine-N-Oxide, and D-amino acids [ 86 , 90 ]. While it is known that there is a gut-kidney cross talk, it has only recently been demonstrated that AKI can influence intestinal microbiomes.…”

Section: The Differences In Gut Microbiota Among Rodents Large Animamentioning

confidence: 99%

Large animal models for translational research in acute kidney injury

et al. 2020

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While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

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

Cited by 109 publications

References 41 publications

d-Amino Acids and Lactic Acid Bacteria

d-Amino Acids and Lactic Acid Bacteria

d-Amino acids and kidney diseases

Large animal models for translational research in acute kidney injury

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