Clinical association between the metabolite of healthy gut microbiota, 3-indolepropionic acid and chronic kidney disease

Sun, Chaomin; Lin, Cheng; Pan, Heng; Lee, Chin Chan; Lü, Shaowu; Hsieh, Yu Ting; Huang, Shih Yi; Huang, Hui Yu

doi:10.1016/j.clnu.2018.11.029

Cited by 48 publications

(40 citation statements)

References 7 publications

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“…p-Cresol sulfate (PCS), one type of protein-bound uremic toxin, is generated by the liver and intestinal bacteria through the metabolic breakdown of tyrosine and phenylalanine. The gut-microbiota metabolite PCS progressively accumulates during the blood circulation of CKD patients due to its high albumin-binding capacity and has been identified as a potential contributor to clinical complications [ 10 , 11 , 12 , 13 ]. In a 5/6 nephrectomy CKD rodent model, the content of PCS is elevated in systemic circulation and the brain tissues, while the increments are decreased by uremic toxin absorbent AST-120 [ 9 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

Sun

Wang

et al. 2020

IJMS

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Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDNF) and serotonin were decreased in association with increased corticosterone and repressor element-1 silencing transcription factor (REST), regulators involved in neurological disorders. On the contrary, these PCS-induced changes were alleviated by uremic toxin absorbent AST-120. Taken together, PCS administration in mice with nephrectomy contributed to neurological disorders with increased oxidative stress and neuroinflammation, which were alleviated by PCS chelation. It is suggested that PCS may be a therapeutic target for chronic kidney disease-associated CNS diseases.

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Section: Introductionmentioning

confidence: 99%

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

Sun

Wang

et al. 2020

IJMS

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Section: Oxygen Incorporated Into Doaa Is Derived From Watermentioning

confidence: 99%

“…However, DOAA with molecular mass of 209 was clearly observed in two cases: when E. coli cells expressing IacAE were used for bioconversion of IAA in H2 18 O environment and with Ox-IAA and IacE-expressing E. coli cells in H2 18 O environment ( Figure 6B). Suspension of E. coli cells in H2 18 O and solution of Ox-IAA in H2 16 O were mixed in a volume ration of 1:1 for the experiments described in Figure 6C, Figure 6A). However, DOAA with molecular mass of 209 was clearly observed in two cases: when E. coli cells expressing IacAE were used for bioconversion of IAA in H 2 18 O environment and with Ox-IAA and IacE-expressing E. coli cells in H 2 O environment ( Figure 6B).…”

Section: Oxygen Incorporated Into Doaa Is Derived From Watermentioning

confidence: 99%

“…Suspension of E. coli cells in H 2 18 O and solution of Ox-IAA in H 2 16 O were mixed in a volume ration of 1:1 for the experiments described in Figure 6C, explaining the presence of [M+H] + ions 208 and 210 with comparable intensities. Taken together, these findings demonstrated that the oxygen atom at C3 in DOAA had originated from water.…”

Section: Oxygen Incorporated Into Doaa Is Derived From Watermentioning

confidence: 99%

“…While indole-3-acetic acid (IAA or heteroauxin) is regarded as the most potent auxin with the strongest plant growth-regulating effects, other auxins that share similar structural scaffold were characterized as well, including indole-3-propionic acid (IPA) and indole-3-butyric acid (IBA) [12]. Surprisingly, the physiological effects of IPA, a product of bacterial tryptophan deamination, has recently been described not only in IPA has been reported to provide beneficial effects for liver functions [15], perform as a biomarker for development of chronic kidney disease [16], and help to reduce the body weight in antibiotictreated mice [17]. In addition, the activity of IPA against M. tuberculosis has been demonstrated [18] and later attributed to the suppression of tryptophan biosynthesis through the inhibition of anthranilate synthetase TrpE [19].…”

Section: Introductionmentioning

confidence: 99%

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Bioconversion of Biologically Active Indole Derivatives with Indole-3-Acetic Acid-Degrading Enzymes from Caballeronia glathei DSM50014

et al. 2020

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A plant auxin hormone indole-3-acetic acid (IAA) can be assimilated by bacteria as an energy and carbon source, although no degradation has been reported for indole-3-propionic acid and indole-3-butyric acid. While significant efforts have been made to decipher the Iac (indole-3-acetic acid catabolism)-mediated IAA degradation pathway, a lot of questions remain regarding the mechanisms of individual reactions, involvement of specific Iac proteins, and the overall reaction scheme. This work was aimed at providing new experimental evidence regarding the biodegradation of IAA and its derivatives. Here, it was shown that Caballeronia glathei strain DSM50014 possesses a full iac gene cluster and is able to use IAA as a sole source of carbon and energy. Next, IacE was shown to be responsible for the conversion of 2-oxoindole-3-acetic acid (Ox-IAA) intermediate into the central intermediate 3-hydroxy-2-oxindole-3-acetic acid (DOAA) without the requirement for IacB. During this reaction, the oxygen atom incorporated into Ox-IAA was derived from water. Finally, IacA and IacE were shown to convert a wide range of indole derivatives, including indole-3-propionic acid and indole-3-butyric acid, into corresponding DOAA homologs. This work provides novel insights into Iac-mediated IAA degradation and demonstrates the versatility and substrate scope of IacA and IacE enzymes.

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A Polyphenol‐Rich Diet Increases the Gut Microbiota Metabolite Indole 3‐Propionic Acid in Older Adults with Preserved Kidney Function

Peron

Meroño

Gargari

et al. 2022

Molecular Nutrition Food Res

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Scope Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim is to study the changes in GM‐derived indoles during a polyphenol‐rich (PR) diet intervention in older adults. Methods and Results Randomized, controlled, crossover trial in adults ≥ 60 years living in a residential care facility during an 8‐week PR versus control diet (n = 51). Seven GM‐tryptophan metabolites are measured in serum, and metataxonomic analysis of GM is performed on fecal samples. Exploratory subgroup analyses are performed based on renal function (RF). The PR‐diet significantly increases serum indole 3‐propionic acid (IPA) in subjects with normal RF, but not in subjects with impaired RF. Other GM‐tryptophan metabolites are not affected. Comparison of baseline GM composition shows shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA are associated with changes in C‐reactive protein (β = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p < 0.001) and Enterobacteriales (r = −0.15, p < 0.05) orders. Conclusion A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults. Trial registration number: ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981).

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Clinical association between the metabolite of healthy gut microbiota, 3-indolepropionic acid and chronic kidney disease

Cited by 48 publications

References 7 publications

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

Bioconversion of Biologically Active Indole Derivatives with Indole-3-Acetic Acid-Degrading Enzymes from Caballeronia glathei DSM50014

A Polyphenol‐Rich Diet Increases the Gut Microbiota Metabolite Indole 3‐Propionic Acid in Older Adults with Preserved Kidney Function

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