Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats

Abstract

van der Wulp MY, Derrien M, Stellaard F, Wolters H, Kleerebezem M, Dekker J, Rings EH, Groen AK, Verkade HJ. Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats. Am J Physiol Gastrointest Liver Physiol 305: G474 -G482, 2013. First published July 18, 2013; doi:10.1152/ajpgi.00375.2012.-Polyethylene glycol (PEG) is a frequently used osmotic laxative that accelerates gastrointestinal transit. It has remained unclear, however, whether PEG affects intestinal functions. We aimed to determine the effect of PEG treatment on intestinal sterol metabolism. Rats were treated with PEG in drinking water (7%) for 2 wk or left untreated (controls). We studied the enterohepatic circulation of the major bile salt (BS) cholate with a plasma stable isotope dilution technique and determined BS profiles and concentrations in bile, intestinal lumen contents, and feces. We determined the fecal excretion of cholesterol plus its intestinally formed metabolites. Finally, we determined the cytolytic activity of fecal water (a surrogate marker of colorectal cancer risk) and the amount and composition of fecal microbiota. Compared with control rats, PEG treatment increased the pool size (ϩ51%; P Ͻ 0.01) and decreased the fractional turnover of cholate (Ϫ32%; P Ͻ 0.01). PEG did not affect the cholate synthesis rate, corresponding with an unaffected fecal primary BS excretion. PEG reduced fecal excretion of secondary BS and of cholesterol metabolites (each P Ͻ 0.01). PEG decreased the cytolytic activity of fecal water [54 (46 -62) vs. 87 (85-92)% erythrocyte potassium release in PEG-treated and control rats, respectively; P Ͻ 0.01]. PEG treatment increased the contribution of Verrucomicrobia (P Ͻ 0.01) and decreased that of Firmicutes (P Ͻ 0.01) in fecal flora. We concluded that PEG treatment changes the intestinal bacterial composition, decreases the bacterial dehydroxylation of primary BS and the metabolism of cholesterol, and increases the pool size of the primary BS cholate in rats.cholate; enterohepatic circulation; bile salt; microbiota POLYETHYLENE GLYCOL (PEG) presently is one of the most widely prescribed laxatives. Long-term treatment with PEG is believed to be safe and highly effective (11,27). However, it is not known whether or not long-term PEG treatment affects specific intestinal metabolic functions. PEG may change the intestinal milieu by accelerating the passage of luminal contents and/or by increasing the luminal water content, possibly leading to a change in the intestinal microflora (10).We have previously shown that PEG treatment accelerates the transit through the small intestine as well as the whole gut in rats (10). PEG decreases fecal excretion of bile salts (BS) in rats (10). BS facilitate the solubilization of lipids (dietary fats, cholesterol, and fat-soluble vitamins) in the small intestine, which is required for efficient lipid absorption (41). It has recently become clear that BS not only are detergents necessary for lip...

Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection

“…Laxatives accelerate gastrointestinal transit time and may have detrimental effects on the intestinal microbiota. van der Wulp et al previously showed that treatment with polyethylene glycol (an osmotic laxative) changes the composition of the intestinal microbiota and decreases the production of secondary bile acids in rats [ 28 ]. We also demonstrated that the use of cephalosporins, fluoroquinolones, and penicillin with β-lactamase inhibitors is significantly and independently associated with reductions in the relative abundance of Clostridiales Family XI Incertae Sedis representatives.…”

Cystic fibrosis mouse model-dependent intestinal structure and gut microbiome

“…The existence of strain-dependent profiles is also likely the reason we were unable to identify specific microbiome constituents which correlated with histological features of intestinal disease in this panel of mice. The intervention used to reduce the incidence of lethal intestinal plugs in the mice, the laxative PEGLYTE, may also have affected the microbiome data observed in CF and WT mice (van der Wulp et al 2013). Finally, although work to document the CF intestinal and pulmonary microbiomes is ongoing (O'Sullivan and Freedman 2009; Sun et al 2014a; Zhao et al 2012, Madan et al 2012), to date increased E. coli levels in fecal samples from CF children (Hoffman et al 2014) and for the lung, CF-associated bacteria including Pseudomonas aeruginosa and Staphylococcus aureus (Goddard et al 2012), as well as Streptococcus and Prevotella (Filkins et al 2012) have been reported, these bacteria were not prominent in the samples from CF mice studied here.…”

The Effect of Chronic Laxative Use on Lipid Profile and HbA1c: A Hospital-Based Retrospective Study

“…Regarding osmotic laxatives, it was found that alteration of the intestinal microbiome composition inhibits the metabolism of the primary bile salts, enhancing its excretion and modifying cholesterol metabolism, which delays its absorption [ 9 ]. Their results were also confirmed later by Strisciuglio et al's (2021) study [ 38 ].…”

“…Moreover, chronic laxative use was reported to be associated with enhanced cholesterol conversion to bile acid and, consequently, lowering the serum level of both cholesterol and low-density lipoprotein-cholesterol (LDL-C) [ 8 ]. Polyethylene glycol (PEG) is an osmotic laxative that regulates cholesterol metabolism and modifies plasma levels [ 9 ]. In addition, the laxative drug elobixibat (an inhibitor of the ileal bile acid transporter) was associated with reduced LDL-C concentration in Japanese patients with chronic constipation [ 10 , 11 ].…”