Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation

Arifuzzaman, Mohammad; Won, Tae Hyung; Li, Tingting; Yano, Hiroshi; Digumarthi, Sreehaas; Heras, Andrea; Zhang, Wen; Parkhurst, Christopher N.; Kashyap, Sanchita; Jin, Wenbing; Putzel, Gregory G.; Tsou, Amy M.; Chu, Coco; Wei, Qianru; Grier, Alex; Longman, Randy S.; Sonnenberg, Gregory F.; Scherl, Ellen; Sockolow, Robbyn; Lukin, Dana J.; Battat, Robert; Ciecierega, Thomas; Solomon, Aliza; Barfield, Elaine; Chien, Kimberley; Ferreira, Johanna; Williams, Jasmin; Khan, Shaira; Chong, Peik Sean; Mozumder, Samah; Chou, Li-Shan; Zhou, Wenqing; Ahmed, Aquil; Zhong, Connie; Joseph, Ann Mary; Gladstone, Joseph; Jensen, Samantha N.; Worgall, Stefan; Guo, Chun-Jun; Schroeder, Frank C.; Artis, David

doi:10.1038/s41586-022-05380-y

Cited by 102 publications

(62 citation statements)

References 80 publications

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“…In vivo studies reported that ingestion of inulin can prevent detrimental phenotypes induced by unbalanced (high-fat/high-sugar) diets, both in humans [ 36 , 37 ] and mice [ 18 , 38 – 40 ], even when administered at very low concentrations [ 41 ]. However, deleterious effects of inulin have also been reported in animals facing intestinal inflammatory conditions [ 42 , 43 ], as well as mice ingesting high doses of this soluble fiber, such as demonstrated by a recent study showing enhanced type 2 inflammation in animals fed with a diet enriched with 26% of inulin [ 44 ]. In vitro and in vivo studies indicated that inulin improves the epithelial barrier, an effect associated with increased expression of tight and adherens junction genes [ 28 , 29 , 39 , 45 – 48 ].…”

Section: Introductionmentioning

confidence: 99%

Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

et al. 2023

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Background The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure. Methods Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment. Results We show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk. Conclusion This study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state.

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Section: Introductionmentioning

confidence: 99%

Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

et al. 2023

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“…This result was consistent with previous findings [ 33 , 34 ]. The increased TBA levels might be related to the significant increase in the amount of Bacteroides , which can secrete bile acid metabolizing enzymes and stimulate the production of bile acids [ 35 ]. As the largest solid organ in the body, the liver is an important place for fat metabolism and maintains a balance between lipid input (lipid uptake and lipogenesis) and output (lipid export and oxidation) [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Obesity Effects of Dietary Fibers Extracted from Flaxseed Cake in Diet-Induced Obese Mice

Zhao

Wang

et al. 2023

Nutrients

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Although many efforts have been made to characterize the functional properties of flaxseed, knowledge concerning the properties of insoluble and soluble dietary fibers in flaxseed is still limited. Here, insoluble and soluble dietary fibers were extracted from flaxseed cake—a valuable resource that has not been fully exploited. Subsequently, their monosaccharide compositions, structural properties, and anti-obesity effects in male mice were characterized. The anti-obesity effects of flaxseed cake insoluble dietary fiber (FIDF), flaxseed cake soluble dietary fiber (FSDF), and FIDF combined with FSDF in diet-induced obese mice were investigated in our study. Supplementation with FSDF alone or FIDF and FSDF together lowered the fat accumulation, improved the serum lipid profile, increased the basal metabolism, and improved the gut microbiota of obese mice. Supplementation with FIDF and FSDF together significantly enriched the abundance of g_Akkermansia and g_Bifidobacterium, which are negatively associated with obesity. Supplementation with FIDF alone improved the liver lipid profile, raised the basal metabolism, and enhanced the short-chain fatty acid levels in the guts of the mice. In conclusion, our results collectively support the therapeutic potential of FIDF and FSDF in obesity treatment and indicate that FIDF and FSDF play different roles in the process of obesity treatment. Furthermore, our results provide critical information for flaxseed cake resource exploitation.

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“…Evidence suggests that SCFAs, as the nal products of dietary ber via intestinal microorganisms, can not only ameliorate the balance of the internal environment but also locally, systematically, and continuously modulate glucose homeostasis, immune cell function and gastrointestinal epithelial cell integrity [1;38]. SCFAs affect a variety of cell types, including regulatory T cells, dendritic cells, and epithelial cells to facilitate immunoregulatory functions in diverse tissues [49][50][51][52]. SCFAs also help regulate innate immunity and reduce colitis, especially propionate, acetate and butyrate, which are bene cial for the integrity of the gastrointestinal barrier [53,54].…”

Section: Discussionmentioning

confidence: 99%

GAP-0 promotes intestinal health by interacting with the gut microbiota to increase energy metabolism

Zhai

et al. 2023

Preprint

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Background Ganoderma applanatum is a well-known edible mushroom whose polysaccharides can improve intestinal health. At present, the mechanism of G. applanatum active polysaccharides and the interactive relationship between gut microbiota active polysaccharides require further investigation. Results We dissected the active ingredient structure and mechanism of the active G. applanatum polysaccharide (GAP). GAP-0 had a →3)-β-Glcp-(1→4)-α-Glcp-(1→ main chain and 6→2)-α-D-Manp-(1→, 6→4)-α-Glcp-(1→4)-α-GalA-(1→, and 6→1)-α-D-Glcp-(6→ side chains. We found that GAP-0 mainly influenced ribosomal large subunit biogenesis, oxidative phosphorylation, ATP metabolic process, ATP synthesis coupled electron transport and generation of precursor metabolites and energy in the colon transcriptome. Through germ-free mouse experiments, we found that GAP-0 was dependent on the gut microbiota. GAP-0 was first utilized by the gut microbiota and demonstrated a protective effect on DSS-induced colitis. In healthy mice, RikenellaceaeRC9 gut group, Bifidobacterium, Oscillibacter and Negativibacillus participated in utilizing GAP-0, and increased short-chain fatty acids (SCFAs) production. The increased acetic acid content was positively related to RikenellaceaeRC9 gut group and Bifidobacterium, valeric acid was positively related to LachnospiraceaeNK4A136 group, RikenellaceaeRC9 gut group and Parasutterella, propionic acid was positively related to Negativibacillus, butyric acid was positively related to Bifidobacterium, isovaleric acid was positively related to Bifidobacterium, and valeric acid was positively related to Negativibacillus. Moreover, Lachnoclostridium, Mucispirillum, Adlercreutzia and GCA900066575 utilized GAP-0 preferentially. Among them Adlercreutzia was positively related to butyric acid and acetic acid, while Mucispirillum was positively related to butyric acid, acetic acid, propionic acid and valeric acid. Conclusions By evaluating the active ingredient structure, GAP-0 was found to mainly improve immunity by increasing energy metabolism. These protective effects were exerted in a gut microbiota-dependent manner. GAP-0 was first utilized by the gut microbiota and showed a protective effect against DSS-induced colitis.

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Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation

Cited by 102 publications

References 80 publications

Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

Anti-Obesity Effects of Dietary Fibers Extracted from Flaxseed Cake in Diet-Induced Obese Mice

GAP-0 promotes intestinal health by interacting with the gut microbiota to increase energy metabolism

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