Intestinal Organoids: A Tool for Modelling Diet–Microbiome–Host Interactions

Rubert, Josep; Schweiger, Pawel J.; Mattivi, Fulvio; Tuohy, Kieran; Jensen, Kim B.; Lunardi, Andrea

doi:10.1016/j.tem.2020.02.004

Cited by 41 publications

(33 citation statements)

References 99 publications

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“…Moreover, to show the direct microbiota-independent effects of pectins on the gastrointestinal immune barrier, it is recommended to perform in vivo studies with germ-free mice, such as those previously performed by Fransen et al, for inulin-type fructans 128 . Furthermore, additional experiments with human intestinal organoid models are needed to further extrapolate these direct effects of pectins on the gastrointestinal immune barrier of humans 129 .…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

2020

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Pectins are dietary fibers with different structural characteristics. Specific pectin structures can influence the gastrointestinal immune barrier by directly interacting with immune cells or by impacting the intestinal microbiota. The impact of pectin strongly depends on the specific structural characteristics of pectin; for example, the degree of methyl-esterification, acetylation and rhamnogalacturonan I or rhamnogalacturonan II neutral side chains. Here, we review the interactions of specific pectin structures with the gastrointestinal immune barrier. The effects of pectin include strengthening the mucus layer, enhancing epithelial integrity, and activating or inhibiting dendritic cell and macrophage responses. The direct interaction of pectins with the gastrointestinal immune barrier may be governed through pattern recognition receptors, such as Toll-like receptors 2 and 4 or Galectin-3. In addition, specific pectins can stimulate the diversity and abundance of beneficial microbial communities. Furthermore, the gastrointestinal immune barrier may be enhanced by short-chain fatty acids. Moreover, pectins can enhance the intestinal immune barrier by favoring the adhesion of commensal bacteria and inhibiting the adhesion of pathogens to epithelial cells. Current data illustrate that pectin may be a powerful dietary fiber to manage and prevent several inflammatory conditions, but additional human studies with pectin molecules with well-defined structures are urgently needed.

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Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

2020

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“…It is important to note that the mechanisms of diet–microbe–host interactions are quite complex and current models are mostly limited to animal models. Intestinal organoids may be a feasible model to overcome such issues [ 180 ]. Besides, the so-called optimal diet may not fit all individuals.…”

Section: Discussionmentioning

confidence: 99%

Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines

Guo

Bian

Liu

et al. 2020

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Trillions of bacteria reside in the human gut and they metabolize dietary substances to obtain nutrients and energy while producing metabolites. Therefore, different dietary components could affect human health in various ways through microbial metabolism. Many such metabolites have been shown to affect human physiological activities, including short-chain fatty acids metabolized from carbohydrates; indole, kynurenic acid and para-cresol, metabolized from amino acids; conjugated linoleic acid and linoleic acid, metabolized from lipids. Here, we review the features of these metabolites and summarize the possible molecular mechanisms of their metabolisms by gut microbiota. We discuss the potential roles of these metabolites in health and diseases, and the interactions between host metabolism and the gut microbiota. We also show some of the major dietary patterns around the world and hope this review can provide insights into our eating habits and improve consumers’ health conditions.

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“…Since hiOs functionally mimic normal human gastrointestinal tract physiology and pathophysiology [151], they represent an effective platform to study human gastrointestinal functions and diseases [154] and are already being successfully employed to model epithelial barrier function [155,156], nutrient transport physiology during digestion [157], celiac disease [158], inflammatory bowel disease [159], and cancer [160][161][162][163]. hiOs provide unprecedented opportunities for the generation of in vitro systems with a sufficient level of complexity to model physiological and pathological diet-microbiome-host conditions [164,165] and pathogen-host interactions [72,155,[166][167][168][169][170][171][172][173][174][175]. Human microbiota suspensions, pathogenic organisms, and/or nutrients can indeed be microinjected into the pseudo-lumen of organoids, which can then be recovered and assayed for microbial composition, microbial transcriptomics, metabolites, and host gene expression profiles (Figure 1).…”

Section: Human Intestinal Organoidsmentioning

confidence: 99%

“…Epithelial organoids (enteroids and colonoids) have been employed to model the effects of diet and nutrients on intestinal growth and development, ion and nutrient transport, secretory and absorption functions, the intestinal barrier, and location-specific functions of the intestine [165]. hiOs responses to gut-microbiota metabolites and microbes could provide novel insights into the mechanisms by which those agents may prevent or trigger diseases, including infections, significantly extending our knowledge of diet-microbiome-host interactions [164]. hiOs are capable of undergoing self-renewal and self-organization for an extended period and replicate many of the physiologically relevant features of the in vivo human intestinal tissue [153].…”

Section: Human Intestinal Organoidsmentioning

confidence: 99%

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

et al. 2020

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The interaction between nutrition and human infectious diseases has always been recognized. With the emergence of molecular tools and post-genomics, high-resolution sequencing technologies, the gut microbiota has been emerging as a key moderator in the complex interplay between nutrients, human body, and infections. Much of the host–microbial and nutrition research is currently based on animals or simplistic in vitro models. Although traditional in vivo and in vitro models have helped to develop mechanistic hypotheses and assess the causality of the host–microbiota interactions, they often fail to faithfully recapitulate the complexity of the human nutrient–microbiome axis in gastrointestinal homeostasis and infections. Over the last decade, remarkable progress in tissue engineering, stem cell biology, microfluidics, sequencing technologies, and computing power has taken place, which has produced a new generation of human-focused, relevant, and predictive tools. These tools, which include patient-derived organoids, organs-on-a-chip, computational analyses, and models, together with multi-omics readouts, represent novel and exciting equipment to advance the research into microbiota, infectious diseases, and nutrition from a human-biology-based perspective. After considering some limitations of the conventional in vivo and in vitro approaches, in this review, we present the main novel available and emerging tools that are suitable for designing human-oriented research.

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Intestinal Organoids: A Tool for Modelling Diet–Microbiome–Host Interactions

Cited by 41 publications

References 99 publications

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

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