scholarly journals High-Fructose Diet Alters Intestinal Microbial Profile and Correlates with Early Tumorigenesis in a Mouse Model of Barrett’s Esophagus

2021 ◽  
Vol 9 (12) ◽  
pp. 2432
Author(s):  
Andrea Proaño-Vasco ◽  
Theresa Baumeister ◽  
Amira Metwaly ◽  
Sandra Reitmeier ◽  
Karin Kleigrewe ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Microbial Communities ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Industrialized Countries ◽  
High Fructose Diet ◽  
Microbial Profile ◽  
High Fructose ◽  
Colon Cancer Cell Lines

Esophageal adenocarcinoma (EAC) is mostly prevalent in industrialized countries and has been associated with obesity, commonly linked with a diet rich in fat and refined sugars containing high fructose concentrations. In meta-organisms, dietary components are digested and metabolized by the host and its gut microbiota. Fructose has been shown to induce proliferation and cell growth in pancreas and colon cancer cell lines and also alter the gut microbiota. In a previous study with the L2-IL-1B mouse model, we showed that a high-fat diet (HFD) accelerated EAC progression from its precursor lesion Barrett’s esophagus (BE) through changes in the gut microbiota. Aiming to investigate whether a high-fructose diet (HFrD) also alters the gut microbiota and favors EAC carcinogenesis, we assessed the effects of HFrD on the phenotype and intestinal microbial communities of L2-IL1B mice. Results showed a moderate acceleration in histologic disease progression, a mild effect on the systemic inflammatory response, metabolic changes in the host, and a shift in the composition, metabolism, and functionality of intestinal microbial communities. We conclude that HFrD alters the overall balance of the gut microbiota and induces an acceleration in EAC progression in a less pronounced manner than HFD.

scholarly journals Dietary Interventions to Prevent High Fructose Diet-associated Worsening of Colitis and Colitis-associated Tumorigenesis in Mice

2021 ◽  
Author(s):  
Ryohei Nishiguchi ◽  
Srijani Basu ◽  
Hannah A Staab ◽  
Naotake Ito ◽  
Xi Kathy Zhou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Experimental Colitis ◽  
Protective Effects ◽  
Diet Change ◽  
Chronic Colitis ◽  
Acute Colitis ◽  
High Fructose Diet ◽  
High Consumption ◽  
High Fructose

Abstract Diet is believed to be an important factor in the pathogenesis of Inflammatory Bowel Disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high fructose diet (HFrD) in experimental colitis. First, we determined whether the pro-colitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared to pectin, inulin or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.

scholarly journals High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yong Wang ◽  
Wentao Qi ◽  
Ge Song ◽  
Shaojie Pang ◽  
Zhenzhen Peng ◽  
...  
Keyword(s):  
Uric Acid ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Lipid Accumulation ◽  
Fasting Blood Glucose ◽  
High Fructose Diet ◽  
Fructose Intake ◽  
High Fructose

High-fructose diet induced changes in gut microbiota structure and function, which have been linked to inflammatory response. However, the effect of small or appropriate doses of fructose on gut microbiota and inflammatory cytokines is not fully understood. Hence, the abundance changes of gut microbiota in fructose-treated Sprague-Dawley rats were analyzed by 16S rRNA sequencing. The effects of fructose diet on metabolic disorders were evaluated by blood biochemical parameter test, histological analysis, short-chain fatty acid (SCFA) analysis, ELISA analysis, and Western blot. Rats were intragastrically administered with pure fructose at the dose of 0 (Con), 2.6 (Fru-L), 5.3 (Fru-M), and 10.5 g/kg/day (Fru-H) for 20 weeks. The results showed that there were 36.5% increase of uric acid level in the Fru-H group when compared with the Con group. The serum proinflammatory cytokines (IL-6, TNF-α, and MIP-2) were significantly increased ( P < 0.05 ), and the anti-inflammatory cytokine IL-10 was significantly decreased ( P < 0.05 ) with fructose treatment. A higher fructose intake induced lipid accumulation in the liver and inflammatory cell infiltration in the pancreas and colon and increased the abundances of Lachnospira, Parasutterella, Marvinbryantia, and Blantia in colonic contents. Fructose intake increased the expressions of lipid accumulation proteins including perilipin-1, ADRP, and Tip-47 in the colon. Moreover, the higher level intake of fructose impaired intestinal barrier function due to the decrease of the expression of tight junction proteins (ZO-1 and occludin). In summary, there were no negative effects on body weight, fasting blood glucose, gut microbiota, and SCFAs in colonic contents of rats when fructose intake is in small or appropriate doses. High intake of fructose can increase uric acid, proinflammatory cytokines, intestinal permeability, and lipid accumulation in the liver and induce inflammatory response in the pancreas and colon.

scholarly journals 860 Development and Characterization of a Surgical, Mouse Model of Reflux Esophagitis and Barrett's Esophagus

2013 ◽  
Vol 144 (5) ◽  
pp. S-1064
Author(s):  
Thai H. Pham ◽  
David H. Wang ◽  
Robert M. Genta ◽  
Rhonda F. Souza ◽  
Stuart J. Spechler
Keyword(s):  
Mouse Model ◽  
Barrett’S Esophagus ◽  
Reflux Esophagitis ◽  
Barrett's Esophagus

scholarly journals 284 – Transgenic Mouse Model Based on Vsig10L, the First Susceptibility Gene for Familial Barrett's Esophagus

2019 ◽  
Vol 156 (6) ◽  
pp. S-57-S-58
Author(s):  
Durgadevi Ravillah ◽  
Anne Baskin ◽  
Nathan A. Berger ◽  
Ronald A. Conlon ◽  
Joseph Willis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Barrett’S Esophagus ◽  
Transgenic Mouse ◽  
Barrett's Esophagus ◽  
Susceptibility Gene ◽  
Transgenic Mouse Model ◽  
Model Based

scholarly journals High Fat-High Fructose Diet-Induced Changes in the Gut Microbiota Associated with Dyslipidemia in Syrian Hamsters

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3557
Author(s):  
Rachael G. Horne ◽  
Yijing Yu ◽  
Rianna Zhang ◽  
Nyan Abdalqadir ◽  
Laura Rossi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Intervention ◽  
High Fat ◽  
Low Fat ◽  
Microbial Composition ◽  
Syrian Hamsters ◽  
High Fructose Diet ◽  
Plasma Triglycerides ◽  
High Fructose ◽  
Induced Changes

Aim: The objective of this study was to characterize the early effects of high fructose diets (with and without high fat) on both the composition of the gut microbiota and lipid metabolism in Syrian hamsters, a reproducible preclinical model of diet-induced dyslipidemia. Methods: Eight-week-old male hamsters were fed diets consisting of high-fat/high-fructose, low-fat/high-fructose or a standard chow diet for 14 days. Stool was collected at baseline (day 0), day 7 and day 14. Fasting levels of plasma triglycerides and cholesterol were monitored on day 0, day 7 and day 14, and nonfasting levels were also assayed on day 15. Then, 16S rRNA sequencing of stool samples was used to determine gut microbial composition, and predictive metagenomics was performed to evaluate dietary-induced shifts in deduced microbial functions. Results: Both high-fructose diets resulted in divergent gut microbiota composition. A high-fat/high-fructose diet induced the largest shift in overall gut microbial composition, with dramatic shifts in the Firmicute/Bacteroidetes ratio, and changes in beta diversity after just seven days of dietary intervention. Significant associations between genus level taxa and dietary intervention were identified, including an association with Ruminococceace NK4A214 group in high-fat/high-fructose fed animals and an association with Butryimonas with the low-fat/high-fructose diet. High-fat/high-fructose feeding induced dyslipidemia with increases in plasma triglycerides and cholesterol, and hepatomegaly. Dietary-induced changes in several genus level taxa significantly correlated with lipid levels over the two-week period. Differences in microbial metabolic pathways between high-fat/high-fructose and low-fat/high-fructose diet fed hamsters were identified, and several of these pathways also correlated with lipid profiles in hamsters. Conclusions: The high-fat/high-fructose diet caused shifts in the host gut microbiota. These dietary-induced alterations in gut microbial composition were linked to changes in the production of secondary metabolites, which contributed to the development of metabolic syndrome in the host.

scholarly journals Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model

2016 ◽  
Vol 311 (3) ◽  
pp. G521-G532 ◽  
Author(s):  
Yueyue Yu ◽  
Lei Lu ◽  
Jun Sun ◽  
Elaine O. Petrof ◽  
Erika C. Claud
Keyword(s):  
Weight Gain ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Preterm Infant ◽  
Microbial Communities ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Stem Cell Marker ◽  
Intestinal Development ◽  
The Impact

Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

scholarly journals Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus

2021 ◽  
Author(s):  
Hsin-Yu Fang ◽  
Stefan Stangl ◽  
Sabrina Marcazzan ◽  
Marcos J. Braz Carvalho ◽  
Theresa Baumeister ◽  
...  
Keyword(s):  
Mouse Model ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Ex Vivo ◽  
Time Lapse ◽  
High Definition ◽  
Specific Detection ◽  
White Light Endoscopy ◽  
Established Risk Factor ◽  
Low Sensitivity

Abstract Purpose The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett’s esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. Methods Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. Results Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized  by human BE dysplastic patient–derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. Conclusion In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.

scholarly journals Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure

2020 ◽  
Vol 21 (15) ◽  
pp. 5488 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
Kay L. H. Wu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Corn Oil ◽  
Male Rat ◽  
Adult Offspring ◽  
Male Adult ◽  
High Fructose Diet ◽  
Fructose Intake ◽  
High Fructose ◽  
Pregnancy And Lactation ◽  
Dioxin Exposure

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure.

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