Effect of Antibiotics and Diet on Enterolactone Concentration and Metabolome Studied by Targeted and Nontargeted LC–MS Metabolomics

Abstract

High plant lignan intake is associated with a number of health benefits, possibly induced by the lignan metabolite enterolactone (ENL). The gut microbiota plays a crucial role in converting dietary lignans into ENL, and epidemiological studies have shown that use of antibiotics is associated with lower levels of ENL. Here we investigate the link between antibiotic use and lignan metabolism in pigs using LC-MS/MS. The effect of lignan intake and antibiotic use on the gut microbial community and the pig metabolome is studied by 16S rRNA sequencing and nontargeted LC-MS. Treatment with antibiotics resulted in substantially lower concentrations of ENL compared with concentrations detected in untreated animals, whereas the plasma concentrations of plant lignans were unchanged. Both diet and antibiotic treatment affected the clustering of urinary metabolites and significantly altered the proportions of taxa in the gut microbiota. Diet, but not antibiotic treatment, affected the plasma lipid profile, and a lower concentration of LDL cholesterol was observed in the pigs fed a high lignan diet. This study provides solid support for the associations between ENL concentrations and use of antibiotics found in humans and indicates that the lower ENL concentration may be a consequence of the ecological changes in the microbiota.

Serum enterolactone concentrations are low in colon but not in rectal cancer patients

“…Thus, we hypothesize that low serum enterolactone concentrations in colon cancer patients may reflect paucity of lignan-converting bacteria in these patients, or an intracolonic environment sub-optimal to bacterial metabolism and lignan conversion. Accordingly, CRC have been linked to gut microbiota dysbiosis 27 and antibiotics are known to reduce circulating enterolactone levels 28,29 . Unfortunately, we do not have data on the frequency of antibiotics usage in our cohort subjects.…”

The role of rye bran and antibiotics on the digestion, fermentation process and short-chain fatty acid production and absorption in an intact pig model

“…Diets, animals, experimental design and microbiota assessments have been described in detail previously in a paper presenting results on plant-and enterolignan concentrations and LC−MS based metabolomics. 18…”

“…17 We have previously demonstrated, that two diets with similar DF content coming from either cellulose or RB induced large differences in plasma and urinary levels of enterolactone and that antibiotic treatment reduced the plasma levels of ENL along with some changes in urinary metabolites presumably caused by the observed ecological changes in microbiota. 18 In this paper, we investigated (1) how the differences in DF structure in the rye bran enriched diet (RB) high in AX and the cellulose enriched diet with similar DF content (CEL) affected nutrient digestibility, NSP degradation and SCFA production and absorption, and (2) whether the modifications of the gut microbiota by the systemic use of antibiotics resulted in changes in carbohydrate degradation and nutrient digestibility of the RB diet. We hypothesised that the AXenriched diet will reduce nutrient digestibility but stimulate fermentation processes, and specifically increase butyrate production and absorption compared with refined wheat fibre, whereas antibiotic treatment will hamper DF degradation and the production of SCFA.…”

Pre-diagnostic plasma enterolactone concentrations are associated with lower mortality among individuals with type 2 diabetes: a case-cohort study in the Danish Diet, Cancer and Health cohort

“…The main dietary sources include seeds, whole grains, nuts and fibre-rich fruits and vegetables, with smaller amounts found in coffee, tea, wine and beer [7]. The metabolism of lignans into enterolignans (enterodiol and enterolactone) is affected by several factors including smoking, obesity, dietary sources of lignans [6], gut microbiota [8] and use of antibiotics [9].…”