2022
DOI: 10.1096/fba.2021-00166
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Human iPSC colon organoid function is improved by exposure to fecal fermentates

Abstract: The host–microbe interaction is critical for intestinal homeostasis. By‐products from microbial metabolism of unabsorbed dietary components have been studied increasingly as potential contributors to health and disease. In vitro fermentation systems provide a way to simulate microbial activity and by‐product production of the colon using human fecal samples. Objectives of the study were to determine how clarified supernatants from two different fermentation conditions affect markers of cell proliferation, diff… Show more

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Cited by 3 publications
(3 citation statements)
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“…One exception was IL-8. Notably, using the same enteroid model, our group has also previously demonstrated an increase in IL-8 due to single SCFA exposure ( Pearce et al, 2020 ) and due to a milleu of fecal metabolites including SCFA ( Pearce et al, 2022 ). In the current study, a significant increase in IL-8 was also observed at the protein level, in addition to a large numeric difference at the gene level with both high butyrate and high acetate treatments.…”
Section: Discussionmentioning
confidence: 82%
See 1 more Smart Citation
“…One exception was IL-8. Notably, using the same enteroid model, our group has also previously demonstrated an increase in IL-8 due to single SCFA exposure ( Pearce et al, 2020 ) and due to a milleu of fecal metabolites including SCFA ( Pearce et al, 2022 ). In the current study, a significant increase in IL-8 was also observed at the protein level, in addition to a large numeric difference at the gene level with both high butyrate and high acetate treatments.…”
Section: Discussionmentioning
confidence: 82%
“…As studying human GI barrier function in vivo is limited by the inaccessibility of the human GI tract, we utilized an intestinal enteroid model that provides a species-specific and physiologically relevant approach to studying mechanisms influencing GI barrier function under controlled environmental conditions and interventions ( Taelman et al, 2022 ). While enteroid models have increasingly been utilized to study the effects of SCFA’s and in vitro fermentation-derived microbial metabolites on the intestinal barrier ( Schilderink et al, 2016 ; Pearce et al, 2020 ; Pace et al, 2021 ; Pearce et al, 2022 ), to our knowledge, these models have not been used to determine the effects of SCFA on intestinal barrier responses to hypoxic stress. We hypothesized that SCFA would improve GI barrier function, reduce the production of pro-inflammatory cytokines, and increase the expression of genes regulating GI barrier function in enteroids exposed to hypoxia and that increasing the proportion of butyrate in the SCFA pool would enhance these benefits.…”
Section: Introductionmentioning
confidence: 99%
“…The use of colon organoids derived from CC and UC patients for studying disease mechanisms and developing individualized therapy strategies has evolved during recent years [ 17 , 18 , 19 , 20 ]. However, studies that investigate the effects of the microbiota on human-derived intestinal organoids are limited [ 21 , 22 , 23 ], and it needs to be determined if external stimuli, such as components and metabolites found in the lumen, are able to induce disease specific phenotypes in organoids derived from healthy human biopsies.…”
Section: Introductionmentioning
confidence: 99%