Dietary fructose improves intestinal cell survival and nutrient absorption

Taylor, Samuel; Ramsamooj, Shakti; Liang, Roger J.; Katti, Alyna; Pozovskiy, Rita; Vasan, Neil; Hwang, Seo-Kyoung; Nahiyaan, Navid; Francoeur, Nancy; Schatoff, Emma M.; Johnson, Jared L.; Shah, Manish A.; Dannenberg, Andrew J.; Sebra, Robert; Dow, Lukas E.; Cantley, Lewis C.; Rhee, Kyu Y.; Goncalves, Marcus D.

doi:10.1038/s41586-021-03827-2

Cited by 144 publications

(108 citation statements)

References 45 publications

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“…Additionally, villus height and crypt depth are key factors that determine intestinal absorption and digestion of nutrients, and their ratio reflects intestinal function ( 33 ). When the intestinal villus height becomes shorter, the absorption area of the intestine decreases, which affects nutrient absorption ( 34 ). This study showed that ETEC K88 can reduce villus height and VH/CD ratio, increase crypt depth, which may affect digestion and absorption in mice.…”

Section: Discussionmentioning

confidence: 99%

Clostridium butyricum Alleviates Enterotoxigenic Escherichia coli K88-Induced Oxidative Damage Through Regulating the p62-Keap1-Nrf2 Signaling Pathway and Remodeling the Cecal Microbial Community

Shang

Liu

et al. 2021

Front. Immunol.

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Clostridium butyricum (CB) can enhance antioxidant capacity and alleviate oxidative damage, but the molecular mechanism by which this occurs remains unclear. This study used enterotoxigenic Escherichia coli (ETEC) K88 as a pathogenic model, and the p62-Keap1-Nrf2 signaling pathway and intestinal microbiota as the starting point to explore the mechanism through which CB alleviates oxidative damage. After pretreatment with CB for 15 d, mice were challenged with ETEC K88 for 24 h. The results suggest that CB pretreatment can dramatically reduce crypt depth (CD) and significantly increase villus height (VH) and VH/CD in the jejunum of ETEC K88-infected mice and relieve morphological lesions of the liver and jejunum. Additionally, compared with ETEC-infected group, pretreatment with 4.4×106 CFU/mL CB can significantly reduce malondialdehyde (MDA) level and dramatically increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum. This pretreatment can also greatly increase the mRNA expression levels of tight junction proteins and genes related to the p62-Keap1-Nrf2 signaling pathway in the liver and jejunum in ETEC K88-infected mice. Meanwhile, 16S rDNA amplicon sequencing revealed that Clostridium disporicum was significantly enriched after ETEC K88 challenge relative to the control group, while Lactobacillus was significantly enriched after 4.4×106 CFU/mL CB treatment. Furthermore, 4.4×106 CFU/mL CB pretreatment increased the short-chain fatty acid (SCFA) contents in the cecum of ETEC K88-infected mice. Moreover, we found that Lachnoclostridium, Roseburia, Lactobacillus, Terrisporobacter, Akkermansia, and Bacteroides are closely related to SCFA contents and oxidative indicators. Taken together, 4.4×106 CFU/mL CB pretreatment can alleviate ETEC K88-induced oxidative damage through activating the p62-Keap1-Nrf2 signaling pathway and remodeling the cecal microbiota community in mice.

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Section: Discussionmentioning

confidence: 99%

Clostridium butyricum Alleviates Enterotoxigenic Escherichia coli K88-Induced Oxidative Damage Through Regulating the p62-Keap1-Nrf2 Signaling Pathway and Remodeling the Cecal Microbial Community

Shang

Liu

et al. 2021

Front. Immunol.

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“…In addition, HFrD feeding is reported to cause colon shortening possibly through endoplasmic reticulum (ER) stress and inflammatory reaction ( Todoric et al, 2020 ). Recently, fructose is found to improve the survival of intestinal villus under hypoxia, resulting in the expanded nutrient absorption of the gut, thus contributing to increased body weight gain and fat accumulation in mice ( Taylor et al, 2021 ). Nonetheless, it is still unclear whether there is an association between the extension of intestinal villi and disordered gut barrier.…”

Section: Dietary Fructose and Intestinal Environmentmentioning

confidence: 99%

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Yu¹,

Li²,

Ji³

et al. 2021

Front. Pharmacol.

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Fructose, especially industrial fructose (sucrose and high fructose corn syrup) is commonly used in all kinds of beverages and processed foods. Liver is the primary organ for fructose metabolism, recent studies suggest that excessive fructose intake is a driving force in non-alcoholic fatty liver disease (NAFLD). Dietary fructose metabolism begins at the intestine, along with its metabolites, may influence gut barrier and microbiota community, and contribute to increased nutrient absorption and lipogenic substrates overflow to the liver. Overwhelming fructose and the gut microbiota-derived fructose metabolites (e.g., acetate, butyric acid, butyrate and propionate) trigger the de novo lipogenesis in the liver, and result in lipid accumulation and hepatic steatosis. Fructose also reprograms the metabolic phenotype of liver cells (hepatocytes, macrophages, NK cells, etc.), and induces the occurrence of inflammation in the liver. Besides, there is endogenous fructose production that expands the fructose pool. Considering the close association of fructose metabolism and NAFLD, the drug development that focuses on blocking the absorption and metabolism of fructose might be promising strategies for NAFLD. Here we provide a systematic discussion of the underlying mechanisms of dietary fructose in contributing to the development and progression of NAFLD, and suggest the possible targets to prevent the pathogenetic process.

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“…Consumption of high-sugar content drinks and products affect the absorption of nutrients such as protein and vitamins, and increase the risk of kidney stones, obesity, diabetes, cardiovascular disease, oral diseases, and even cancers (Bantle et al 2009 ; Delli Bovi et al 2017 ; Febbraio et al 2021 ; Johnson et al 2018 ; Kohn et al 2017 ; Taylor et al 2021 ). To promote development of the low-sugar-content industry, many countries and regions have propagated and promoted sugar reduction to be under mandatory national control, and have also gradually formulated and promulgated the taxation policy for high-sugar-content foods.…”

Section: Introductionmentioning

confidence: 99%

Revitalizing the ethanologenic bacterium Zymomonas mobilis for sugar reduction in high-sugar-content fruits and commercial products

Chen

Huang

et al. 2021

Bioresour. Bioprocess.

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The excessive consumption of sugars can cause health issues. Different strategies have been developed to reduce sugars in the diets. However, sugars in fruits and commercial products may be difficult to reduce, limiting their usage among certain populations of people. Zymomonas mobilis is a generally recognized as safe (GRAS) probiotic bacterium with the capability to produce levan-type prebiotics, and thrives in high-sugar environments with unique characteristics to be developed for lignocellulosic biofuel and biochemical production. In this study, the sugar reduction capabilities of Z. mobilis ZM4 were examined using two fruits of pear and persimmon and three high-sugar-content commercial products of two pear pastes (PPs) and one Chinese traditional wine (CTW). Our results demonstrated that Z. mobilis ZM4 can utilize sugars in fruits with about 20 g/L ethanol and less than 5 g/L sorbitol produced within 22 h using pears, and about 45 g/L ethanol and 30 g/L sorbitol produced within 34 h using persimmons. When PPs made from pears were used, Z. mobilis can utilize nearly all glucose (ca. 60 g/L) and most fructose (110 g/L) within 100 h with 40 ~ 60 g/L ethanol and more than 20 g/L sorbitol produced resulting in a final sorbitol concentration above 80 g/L. In the high-sugar-content alcoholic Chinese traditional wine, which contains mostly glucose and ethanol, Z. mobilis can reduce nearly all sugars with about 30 g/L ethanol produced, resulting in a final ethanol above 90 g/L. The ethanol yield and percentage yield of Z. mobilis in 50 ~ 60% CTW were 0.44 ~ 0.50 g/g and 86 ~ 97%, respectively, which are close to its theoretical yields—especially in 60% CTW. Although the ethanol yield and percentage yield in PPs were lower than those in CTW, they were similar to those in fruits of pears and persimmons with an ethanol yield around 0.30 ~ 0.37 g/g and ethanol percentage yield around 60 ~ 72%, which could be due to the formation of sorbitol and/or levan in the presence of both glucose and fructose. Our study also compared the fermentation performance of the classical ethanologenic yeast Saccharomyces cerevisiae BY4743 to Z. mobilis, with results suggesting that Z. mobilis ZM4 had better performance than that of yeast S. cerevisiae BY4743 given a higher sugar conversion rate and ethanol yield for sugar reduction. This work thus laid a foundation for utilizing the advantages of Z. mobilis in the food industry to reduce sugar concentrations or potentially produce alcoholic prebiotic beverages. Graphical Abstract

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Dietary fructose improves intestinal cell survival and nutrient absorption

Cited by 144 publications

References 45 publications

Clostridium butyricum Alleviates Enterotoxigenic Escherichia coli K88-Induced Oxidative Damage Through Regulating the p62-Keap1-Nrf2 Signaling Pathway and Remodeling the Cecal Microbial Community

Clostridium butyricum Alleviates Enterotoxigenic Escherichia coli K88-Induced Oxidative Damage Through Regulating the p62-Keap1-Nrf2 Signaling Pathway and Remodeling the Cecal Microbial Community

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Revitalizing the ethanologenic bacterium Zymomonas mobilis for sugar reduction in high-sugar-content fruits and commercial products

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