This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70–80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells.

La microbiota intestinal (MI) es considerada como un nuevo blanco para la prevención y manejo nutricional de las alteraciones inflamatorias y metabólicas asociadas a las enfermedades crónicas no-transmisibles. Los prebióticos son principalmente fibras solubles cuyo consumo favorece el crecimiento de poblaciones bacterianas beneficiosas de la MI e impacta favorablemente la salud del consumidor. Esta revisión presenta a los fitoquímicos dietarios, que incluyen a más de 8.000 compuestos, como una nueva clase de prebióticos debido a su capacidad de estimular poblaciones de Lactobacillus, Bifidobacterium, Akkermansia y de bacterias productoras de butirato en el colon, a expensa de bacterias potencialmente dañinas como C. histolyticum. Además, los fitoquímicos son transformados por la MI en múltiples metabolitos que ejercen actividades biológicas a veces más potentes que la molécula inicial de la cual provienen. Individuos con distintos metabotipos han sido descritos de acuerdo a su capacidad de responder al consumo de isoflavonas, lignanos o elagitaninos, dependiendo de la presencia en su MI de bacterias capaces de transformar dichos polifenoles en equol, enterolactona/enterodiol y urolitinas, respectivamente, los cuales exhiben actividades biológicas. Valerolactonas y ácidos aromáticos también son producidos por la MI a través del metabolismo de las proantocianidinas. El efecto prebiótico de los fitoquímicos contribuiría a explicar los efectos saludables del consumo de frutas y verduras ricos en fitoquímicos.

Low DM-pectins have strong anti-inflammatory effects and prevents dysregulation of TJ-related genes. The effects of pectin are dependent on DM of the pectin, the magnitude of TLR2 expression and on circulating sTLR2 in blood.

Pancreatic islet transplantation offers great promise for the treatment of type 1 diabetes, yet the functional decline of islets after isolation remains a major obstacle. Increasing evidence highlights the endoplasmic reticulum (ER) as a critical regulator of islet cell survival under stress. We explored how ex vivo culture conditions affect encapsulated islet resilience under ER-stress. Two conditions were assessed: (i) incorporation of decellularized porcine pancreatic extracellular matrix (ECM) into alginate microcapsules, and (ii) free-fall dynamic pre-conditioning culture. Human islets were encapsulated in alginate with or without ECM, cultured under static or dynamic conditions, and exposed to acute ER-stress followed or not by a recovery period. Dynamic culture preserved viability and enhanced glucose responsiveness. ECM-containing capsules showed reduced inflammatory marker expression, while encapsulation in alginate-only capsules led to more pronounced changes associated with ECM remodeling. Under ER-stress, the dynamic culture, especially combined with ECM, maintained cell function and reduced cell death. Gene profiles indicated improved stress adaptation and ECM remodeling. These results highlight ECM enrichment and dynamic culture as good strategies to maintain islet survival and functionality.

The intestinal barrier is a dynamic interface integrating epithelial integrity, mucus architecture, and immune signaling to maintain host homeostasis. While microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan derivatives regulate this system, translating these insights to human physiology is hindered by experimental models that fail to capture the intestine’s full biological complexity. In this review, we conceptualize intestinal barrier failure as a sequential process comprising junctional remodeling, mucus depletion, and immune-driven permeability. We critically evaluate current in vitro and ex vivo models, highlighting how metabolic biases and reductionist designs in common platforms limit their predictive value. We argue that the primary bottleneck is not a lack of model diversity, but the absence of integrative, human-relevant strategies. Consequently, we propose a stepwise framework linking dynamic microbial fermentation to mechanistic epithelial systems and ex vivo human tissues. This approach moves beyond descriptive modeling toward functionally predictive platforms that align microbial metabolism with host responses across biological scales, ultimately informing clinical translation, precision nutrition, and therapeutic development.