Presentation Authors: Paul Dominguez Gutierrez*, Pedro Espino-Grosso, Raghav Pai, William Donelan, Benjamin Canales, Gainesville, FL
Introduction: Absorptive hypercalciuria, or excessive gut absorption of dietary calcium, is the most commonly identified metabolic cause of calcium-based renal stones. Since intestinal commensal bacteria are known to play an integral role in nutrient metabolism, we hypothesized that gut microbiota may affect calcium absorption and tested this using an antibiotic rodent model.
Methods: Young, pathogen-free Sprague-Dawley rats were evenly distributed into untreated controls (UTX; n=12), chloramphenicol-treated (CTX; n=12) and neomycin-treated (NEO; n=12) groups. Urine and feces were collected in metabolic cages before (baseline) and after (1 week, 4 weeks) a 7 day course of 0.07% oral antibiotic treatment in sterile water. Rats received identical amounts of food quantity during collection periods and ad-libitum amounts during the remainder of the protocol. Serum calcium, phosphate, and albumin were measured at 4 weeks on an automated chemistry analyzer. Rat intact PTH, circulating bone turnover markers (BTM), and serum 25(OH)D were measured using commercially available kits. 24-hour urine and fecal calcium samples were analyzed at Litholink Corporation. Intestinal microbiota were chacterized by 16S rRNA Illumina paired-end sequencing, and QIIME and metaGenomeSeq software were used to analyze microbial community differences.
Results: At one week, both male and female CTX animals showed a reversible, 3-fold increase in urinary calcium excretion coupled with a 25% increase in intestinal calcium absorption. These changes resulted in two-fold increase in calcium oxalate and phosphate urinary supersaturation. No differences were observed in serum labs, BTM, PTH, or vitamin D among the three groups. CTX microbial communities were markedly different from UTX and NEO groups by heat-map and discriminant plotting (Figure a/b).
Conclusions: In our model, one week of chloramphenicol caused increased intestinal gut calcium absorption and resultant urinary calcium excretion without changes in circulating measures of bone and mineral homeostasis. Gut microbiome was markedly different between the three groups. Should these findings be validated in future studies, functional study of the gut microbial communities responsible for these changes may allow us to target and treat the gut microbiota responsible for absorptive hypercalciuria.
Source of Funding: NIH T32-DK094789