Modulation of Gut Microbiota by Glucosamine and Chondroitin in a Randomized, Double-Blind Pilot Trial in Humans

Abstract

Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&C are poorly absorbed and therefore metabolized by gut microbiota. G&C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate < 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.

Impact of Glucosamine Supplementation on Gut Health

“…The reduction in bacterial alpha-diversity (a metric of the total bacterial contents in the fecal samples) with the inclusion of glucosamine in the diet is consistent with previous reports where both glucosamine and chondroitin [26] or glucosamine and green lipped muscle extract [25] were consumed. However, our other findings differed from these studies including a lack of an effect on bacterial beta-diversity and differences between the affected taxa compared with those prior reports.…”

“…Comparisons of the baseline samples indicated significant variations in the abundance of Enterococcaceae and Lactococcus suggesting that other factors may determine the levels of these taxa in the distal intestine. While Navarro et al [ 26 ] recruited healthy subjects, the differences in the supplementation protocol (14 vs. 21 days, combination of glucosamine + chondroitin vs. glucosamine alone, 1500 mg vs. 3000 mg dose and frequency of glucosamine, and the source of glucosamine (shellfish-derived vs. fermentation)) may have led to differences in our observed outcomes.…”

“…However, greater conclusions from this study are underpinned by its lack of a placebo or appropriate control group. Most recently, Navarro et al [ 26 ] observed that oral co-administration of glucosamine hydrochloride (derived from crab and shrimp) and chondroitin sulfate significantly modulated nine different genera after a 14-day supplementation using a placebo-controlled, crossover design. Specifically, abundances of Lachnospiraceae , Prevotellaceae , and Desulfovibrio were increased while Bifidobacterium and Christensenellaceae were decreased.…”

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry

“…Our data suggest that observed differences in ENL production and microbiome composition between AA and EA could be relevant to population-specific differences in chronic disease prevalence. For example, cross-sectional studies have reported an inverse relationship between ENL excretion and circulating secondary bile acids [ 63 , 64 ], bacterial metabolites associated with increased risk of CVD, cirrhosis [ 65 ], and CRC [ 45 , 64 ]. In our study, Lachnoclostridium was inversely associated with ENL production in EA.…”

“…In our study, Lachnoclostridium was inversely associated with ENL production in EA. Lachnoclostridium includes species involved in the 7α-dehydroxylation of cholic acid to the secondary bile acid dehydroxycholic acid (DCA) [ 66 ], and a recent metagenomic analysis demonstrated that ENL-producing microbial consortia also expressed genes involved in secondary bile acid metabolism [ 63 ]. Further exploration is needed to investigate whether a diet high in lignans may alter the microbiome sufficiently to reduce the exposure to the amount and type of secondary bile acids linked to disease risk.…”