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Rifaximin Effects on Serum Trimethylamine‐n‐oxide in Chronic Kidney Disease
Author(s) -
Johnson Cassi,
Zhang Shiqin,
Omede Faith,
Stubbs Jason
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1030.19
Subject(s) - rifaximin , kidney disease , medicine , trimethylamine n oxide , gastroenterology , endocrinology , chemistry , antibiotics , trimethylamine , biochemistry
Trimethylamine‐n‐oxide (TMAO) is a byproduct of intestinal bacteria metabolism of choline and L‐carnitine. In patients with chronic kidney disease (CKD), TMAO accumulates in the bloodstream and is thought to perpetuate kidney fibrosis and promote cardiovascular disease (CVD). We hypothesized that rifaximin, a broad‐spectrum oral antibiotic with poor bioavailability, would significantly lower serum TMAO levels and slow kidney disease progression in CKD mice. Design CKD mice were generated by feeding C57BL/6J mice a diet containing 0.2% adenine; non‐CKD mice received the same diet without adenine supplementation. To test whether acute rifaximin therapy could lower serum TMAO levels, mice were fed the 0.2% adenine or control diet for 7 weeks. Starting at week 6 of the study, mice were randomized to receive 50 mg/kg rifaximin or vehicle once daily for the final week. In a separate study to assess whether long‐term rifaximin therapy could lower serum TMAO levels and attenuate kidney disease, 50 mg/kg rifaximin or vehicle therapy was administered 5 days/week (M‐F) at the onset of CKD induction by 0.2% adenine diet and continued for 13 weeks. Results Acute rifaximin therapy lowered post‐treatment serum TMAO levels in both non‐CKD (0.76 ±0.41 μM for rifaximin vs 3.78±1.45 μM for vehicle; p=NS) and CKD mice (8.91±2.20 μM for rifaximin vs 15.92±1.67 μM for vehicle; p<0.01). We observed shifts in microbiome composition with rifaximin therapy reflected by a decrease in microbiome diversity when comparing stool samples collected pre‐ and post‐rifaximin treatment that could account for decreased serum TMAO (Shannon H test: 2.51±0.01 for rifaximin vs 3.42±0.15 for vehicle in non‐CKD mice; 2.37±0.09 for rifaximin vs 3.53±0.25 for vehicle in CKD mice). However, long‐term rifaximin therapy did not lower serum TMAO levels in non‐CKD (6.87±1.13 uM for rifaximin vs 10.21±1.58 for vehicle; p=NS) or CKD mice (41.08±5.78 for rifaximin vs 45.51±3.89 for vehicle; p=NS). Likewise, rifaximin therapy failed to alter CKD progression as assessed by both serum markers of renal function and gene markers of kidney fibrosis. Conclusion Our data suggests that rifaximin therapy may be a viable option for short‐term lowering of serum TMAO in CKD; however, long‐term administration of this drug does not sustain this TMAO‐lowering effect or alter CKD progression in mice.