Oats and rye regulate lipid metabolism through different mechanisms and improve liver function and intestinal barrier function.


【Introduction】
It is widely known that dietary fiber regulates the intestinal environment, suppresses inflammation, and improves sugar and lipid metabolism, but whether different types of dietary fiber have different metabolites and host responses in the intestine remains elucidated. In this study, we investigated the effects of the consumption of β-glucan-rich oats and arabinoxylan-rich rye on the metabolism of tryptophan, which is involved in glucose and lipid metabolism, production of short-chain fatty acids, liver function, and intestinal barrier function.

【Materials and Methods】
Normal male mice (C57BL/6N) aged 3-4 weeks were divided into four groups (12 mice per group) fed the following diets for 17 weeks: CHOW, WD, OAT, and RYE.
CHOW: standard control diet
WD: high-fat diet
OAT: High-fat diet containing 10% oat bran (3% β-glucan).
RYE: High-fat diet containing 10% rye bran (3.5% arabinoxylan).

Bodyweight was recorded weekly, body composition was measured at 15 weeks, and glucose and insulin tolerance tests were performed at 15 and 16 weeks. Bodyweight was recorded weekly, body composition was measured at 15 weeks, and glucose tolerance and insulin tolerance tests were performed at 15 and 16 weeks. At the end of the rearing period, the animals were dissected, and various biochemical tests were performed. The amount of bile acids in ileum and feces, and the amount of short-chain fatty acids in the cecum were measured, the expression of genes involved in liver inflammation, intestinal barrier function, and tryptophan metabolism was analyzed, and histological examination of liver and adipose tissue (upper part of testis) was performed.

【Results】
Bodyweight and body composition
Compared to WD, weight gain was suppressed in OAT and RYE, especially in RYE. The body fat percentage and lean body mass of OAT and RYE were similar to those of WD.

Liver function and intestinal barrier function
The increase in ALT and AST, which are indicators of liver function, was suppressed in OAT and RYE compared to WD. This inhibitory effect correlated with the suppression of mRNA expression levels of TNF and TLR4 (Toll-like receptor 4), which are indicators of inflammation in the liver.

The mRNA expression levels of mucin (Muc3) and tight junction-related proteins (occludin, claudin-7) in the colon were higher in OAT and RYE than in WD, suggesting an improvement in the barrier function of the intestine.

OAT and RYE suppressed neither liver hypertrophy nor the accumulation of triglycerides in the liver in WD. However, adipocytes in the liver tended to be smaller in OAT and RYE than in WD. The weight of the cecum, an indicator of intestinal bacterial activity, was heavier in OAT and RYE than in WD.

Glucose and lipid metabolism
Fasting blood glucose levels were lower in OAT than in WD, but RYE was similar to WD. The insulin tolerance test results and glucose tolerance test were similar in WD, OAT, and RYE groups.

Serum triglyceride levels were lower in OAT than in WD, but LDL and HDL levels were similar, and the HDH/LDL ratio was higher than in WD.

Short-chain fatty acids in the cecum
The acetic acid, butyric acid, and propionic acid in the cecum were higher in both OAT and RYE than in WD.

mRNA expression levels in the ileum
Tryptophan is catabolized to indole by intestinal bacteria and promotes the production of interleukin-22 via the aryl carbon-hydrogen receptor (AHR), thereby improving the immune response through tight junction proteins, antimicrobial compounds and mucins *1 *2.

TPH-1, an enzyme that metabolizes tryptophan to serotonin, was elevated in WD but suppressed OAT and RYE. The expression of AHR was inversely correlated with that of TPH-1 and suppressed in WD. The expression of interleukin-22 was also high in OAT and RYE, especially in OAT. The expression of TPH-1 was inversely correlated with the concentration of short-chain fatty acids in the ileum, especially propionic acid.

Bile acids in ileum and feces
The binding of bile acids to FXR, a nuclear receptor highly expressed in the liver and ileum, inhibits the activity of CYP7a1, an enzyme required for the synthesis of bile acids from cholesterol, resulting in decreased production of bile acids (and consequent accumulation of cholesterol).

Compared to WD, OAT and RYE showed lower mRNA expression of FXR in the ileum and higher mRNA expression of CYP7a1 in the liver. The ratio of tauro-β-muricholic acid (T-βMCA), which acts as a potent antagonist of FXR in the ileum, was significantly higher in OAT than in the other groups. The ratio of T-βMCA to total bile acids, which act as agonists of FXR, showed a similar pattern. On the other hand, the number of conjugated bile acids in the feces of RYE was higher than that of OAT.

Intestinal microflora
The results showed that Bacteroidetes/Firmicutes were higher in OAT and RYE than WD; the proportion of Proteobacteria was lower than in WD, and that of Saccharibacteria was higher in OAT. The proportion of Bacteroidetes was slightly higher in OAT and RYE than in WD (higher in RYE than in OAT), and Firmicutes was lower in OAT. OAT had a high proportion of Lactobacillus at the genus level, and RYE had a high proportion of Bifidobacterium.

【Discussion and Conclusion】
Dietary fiber from oats and rye was shown to inhibit weight gain due to high-fat food loading, promote the production of short-chain fatty acids, regulate the intestinal environment, reduce liver inflammation, and enhance intestinal barrier function.

The decrease in the mRNA expression level of TPH-1 in OAT and RYE was inversely correlated with the amount of short-chain fatty acids, suggesting that short-chain fatty acids may be involved in the activity of endogenous enzymes as well as intestinal bacteria. Dietary fiber deficiency promotes the conversion of tryptophan to serotonin and suppresses its conversion to indole, resulting in a reduced immune response by interleukin-22. This imbalance may have been adjusted by increased short-chain fatty acid levels and intestinal microflora changes due to oats and rye consumption, but further investigation is needed.

【Research institution】
The University of Hong Kong (Hong Kong)
University of Eastern Finland (Finland)
Kuopio University Hospital (Finland)
VTT Finnish Technology Research Centre (Finland)

*1 Gastroenterology 141, 1, 237-48, 2011
*2 J Mol Biol 427, 23, 3676-82, 2015


Dietary Fiber from Oat and Rye Brans Ameliorate Western Diet–Induced Body Weight Gain and Hepatic Inflammation by the Modulation of Short-Chain Fatty Acids, Bile Acids, and Tryptophan Metabolism
Mol Nutr Food Res e1900580, 2020