Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6
ABSTRACT Renal calcium oxalate (CaOx) stone is a common urologic disease with a high prevalence and recurrence rate. However, short-chain fatty acids (SCFAs) are less often reported in the prevention of urolithiasis. This study aimed to explore the effect of SCFAs on the renal CaOx stone formation a...
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American Society for Microbiology
2021-12-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.01045-21 |
| _version_ | 1818979332620550144 |
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| author | Yu Liu Xi Jin Yucheng Ma Zhongyu Jian Zhitao Wei Liyuan Xiang Qun Sun Shiqian Qi Kunjie Wang Hong Li |
| author_facet | Yu Liu Xi Jin Yucheng Ma Zhongyu Jian Zhitao Wei Liyuan Xiang Qun Sun Shiqian Qi Kunjie Wang Hong Li |
| author_sort | Yu Liu |
| collection | DOAJ |
| description | ABSTRACT Renal calcium oxalate (CaOx) stone is a common urologic disease with a high prevalence and recurrence rate. However, short-chain fatty acids (SCFAs) are less often reported in the prevention of urolithiasis. This study aimed to explore the effect of SCFAs on the renal CaOx stone formation and the underlying mechanisms. Ethylene glycol was used to induce renal CaOx crystals in rats. SCFAs (acetate, propionate, or butyrate) were added as supplements to the drinking water with or without antibiotics. Because intestinal oxalate transporters SLC26A6 and SLC26A3 regulate the excretion and absorption of oxalate in the intestine, we injected adeno-associated virus 9 (AAV9)-SLC26A6-shRNA (short hairpin RNA) and AAV9-SLC26A3 into the tail vein of rats to suppress SLC26A6 and overexpress SLC26A3 expression in the intestine, respectively, to explore the role of SLC26A3 and SLC26A6 (SLC26A3/6) in the reduction of renal CaOx crystals induced by SCFAs. Results showed that SCFAs reduced renal CaOx crystals and urinary oxalate levels but, however, increased the abundance of SCFA-producing bacteria and cecum SCFA levels. SCFA supplements still reduced renal crystals and urinary oxalate after gut microbiota depletion. Propionate and butyrate downregulated intestinal oxalate transporter SLC26A3 expression, while acetate and propionate upregulated SLC26A6 expression, both in vivo and in vitro. AAV9-SLC26A3 exerted a protective effect against renal crystals, while AAV9-SLC26A6-shRNA contributed to the renal crystal formation even though the SCFAs were supplemented. In conclusion, SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones. IMPORTANCE Some studies found that the relative abundances of short-chain-fatty-acid (SCFA)-producing bacteria were lower in the gut microbiota of renal stone patients than healthy controls. Our previous study demonstrated that SCFAs could reduce the formation of renal calcium oxalate (CaOx) stones, but the mechanism is still unknown. In this study, we found that SCFAs (acetate, propionate, and butyrate) reduced the formation of renal calcium oxalate (CaOx) crystals and the level of urinary oxalate. Depleting gut microbiota increased the amount of renal crystals in model rats, and SCFA supplements reduced renal crystals and urinary oxalate after gut microbiota depletion. Intestinal oxalate transporter SLC26A6 was a direct target of SCFAs. Our findings suggested that SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones. |
| first_indexed | 2024-12-20T16:57:51Z |
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| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-20T16:57:51Z |
| publishDate | 2021-12-01 |
| publisher | American Society for Microbiology |
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| series | mSystems |
| spelling | doaj.art-00ada19838b346898688a636928da7572022-12-21T19:32:41ZengAmerican Society for MicrobiologymSystems2379-50772021-12-016610.1128/mSystems.01045-21Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6Yu Liu0Xi Jin1Yucheng Ma2Zhongyu Jian3Zhitao Wei4Liyuan Xiang5Qun Sun6Shiqian Qi7Kunjie Wang8Hong Li9Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaKey Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaABSTRACT Renal calcium oxalate (CaOx) stone is a common urologic disease with a high prevalence and recurrence rate. However, short-chain fatty acids (SCFAs) are less often reported in the prevention of urolithiasis. This study aimed to explore the effect of SCFAs on the renal CaOx stone formation and the underlying mechanisms. Ethylene glycol was used to induce renal CaOx crystals in rats. SCFAs (acetate, propionate, or butyrate) were added as supplements to the drinking water with or without antibiotics. Because intestinal oxalate transporters SLC26A6 and SLC26A3 regulate the excretion and absorption of oxalate in the intestine, we injected adeno-associated virus 9 (AAV9)-SLC26A6-shRNA (short hairpin RNA) and AAV9-SLC26A3 into the tail vein of rats to suppress SLC26A6 and overexpress SLC26A3 expression in the intestine, respectively, to explore the role of SLC26A3 and SLC26A6 (SLC26A3/6) in the reduction of renal CaOx crystals induced by SCFAs. Results showed that SCFAs reduced renal CaOx crystals and urinary oxalate levels but, however, increased the abundance of SCFA-producing bacteria and cecum SCFA levels. SCFA supplements still reduced renal crystals and urinary oxalate after gut microbiota depletion. Propionate and butyrate downregulated intestinal oxalate transporter SLC26A3 expression, while acetate and propionate upregulated SLC26A6 expression, both in vivo and in vitro. AAV9-SLC26A3 exerted a protective effect against renal crystals, while AAV9-SLC26A6-shRNA contributed to the renal crystal formation even though the SCFAs were supplemented. In conclusion, SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones. IMPORTANCE Some studies found that the relative abundances of short-chain-fatty-acid (SCFA)-producing bacteria were lower in the gut microbiota of renal stone patients than healthy controls. Our previous study demonstrated that SCFAs could reduce the formation of renal calcium oxalate (CaOx) stones, but the mechanism is still unknown. In this study, we found that SCFAs (acetate, propionate, and butyrate) reduced the formation of renal calcium oxalate (CaOx) crystals and the level of urinary oxalate. Depleting gut microbiota increased the amount of renal crystals in model rats, and SCFA supplements reduced renal crystals and urinary oxalate after gut microbiota depletion. Intestinal oxalate transporter SLC26A6 was a direct target of SCFAs. Our findings suggested that SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones.https://journals.asm.org/doi/10.1128/mSystems.01045-21renal calcium oxalate stonesshort-chain fatty acidsintestinal oxalate transportersgut microbiotaoxalate |
| spellingShingle | Yu Liu Xi Jin Yucheng Ma Zhongyu Jian Zhitao Wei Liyuan Xiang Qun Sun Shiqian Qi Kunjie Wang Hong Li Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 mSystems renal calcium oxalate stones short-chain fatty acids intestinal oxalate transporters gut microbiota oxalate |
| title | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 |
| title_full | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 |
| title_fullStr | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 |
| title_full_unstemmed | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 |
| title_short | Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6 |
| title_sort | short chain fatty acids reduced renal calcium oxalate stones by regulating the expression of intestinal oxalate transporter slc26a6 |
| topic | renal calcium oxalate stones short-chain fatty acids intestinal oxalate transporters gut microbiota oxalate |
| url | https://journals.asm.org/doi/10.1128/mSystems.01045-21 |
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