Butyrate modulates antioxidant enzyme expression in malignant and non‐malignant human colon tissues

Abstract

The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.

Chemopreventive potential of in vitro fermented nuts in LT97 colon adenoma and primary epithelial colon cells

“…Former studies indicated that the induction of these genes can be attributed to butyrate as the key fermentation product of dietary fiber. 28,35,41,42 Though there is no direct link between the daily recommended nut intake and FS used in the present study, we could recently confirm that the fermentation of nuts results in up to 2.8-fold higher concentrations of short chain fatty acids compared to the control and a shift of molar ratios towards butyrate production ranging in physiological observed FIGURE 3 Growth inhibiting of LT97 colon adenoma cells after incubation with fermented nut samples and controls (blank, Synergy1®) in concentrations of 2.5-20% for 24 h (a), 48 h (b), and 72 h (c) (mean + SD, n = 3). Significant differences between blank and fermentation supernatants (FS) of Synergy1® or nuts (***P ≤ 0.001, **P ≤ 0.01, *P ≤ 0.05) and between FS ( a-e P ≤ 0.05, equal letters represent significant differences) were obtained by two-way Anova/Bonferroni post-test.…”

Immune Modulation by Microbiota Sources: Effects of Aloe vera gel and Butyrate

“…Jahns et al [31] investigated the effect of a butyrate treatment on catalase and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages ex vivo. Despite a significantly lowered SOD2 transcript and to a lesser extent of protein level after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced, suggesting an increased protection against tissue superoxide radicals.…”

Nature vs. Nurture: The Gut Microbiome and Genetics in the Development of Gastrointestinal Disease

“…Butyrate is responsible for a number of physiologic roles within the gastrointestinal tract, including maintenance of intestinal barrier integrity, regulation of epigenetic gene expression, and mediation of anti-inflammatory responses to oxidative stress [95][96][97]. Alterations of butyrate producing species have been noted in both UC and CD patients with somewhat differing roles.…”