Browsing by Subject "Intestinal barrier"

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Cognitive alterations in old mice are associated with intestinal barrier dysfunction and induced toll-like receptor 2 and 4 signaling in different brain regions
(2023) Brandt, Annette; Kromm, Franziska; Hernández-Arriaga, Angélica; Martínez Sánchez, Inés; Bozkir, Haktan Övül; Staltner, Raphaela; Baumann, Anja; Camarinha-Silva, Amélia; Heijtz, Rochellys Diaz; Bergheim, Ina
Emerging evidence implicate the ‘microbiota–gut–brain axis’ in cognitive aging and neuroinflammation; however, underlying mechanisms still remain to be elucidated. Here, we assessed if potential alterations in intestinal barrier function and microbiota composition as well as levels of two key pattern-recognition receptors namely Toll-like receptor (TLR) 2 and TLR4, in blood and different brain regions, and depending signaling cascades are paralleling aging associated alterations of cognition in healthy aging mice. Cognitive function was assessed in the Y-maze and intestinal and brain tissue and blood were collected in young (4 months old) and old (24 months old) male C57BL/6 mice to determine intestinal microbiota composition by Illumina amplicon sequencing, the concentration of TLR2 and TLR4 ligands in plasma and brain tissue as well as to determine markers of intestinal barrier function, senescence and TLR2 and TLR4 signaling. Cognitive function was significantly impaired in old mice. Also, in old mice, intestinal microbiota composition was significantly altered, while the relative abundance of Gram-negative or Gram-positive bacteria in the small and large intestines at different ages was not altered. Moreover, intestinal barrier function was impaired in small intestine of old mice, and the levels of TLR2 and TLR4 ligands were also significantly higher in both portal and peripheral blood. Furthermore, levels of TLR2 and TLR4 ligands, and downstream markers of TLR signaling were higher in the hippocampal and prefrontal cortex of old mice compared to young animals. Taken together, our results suggest that even in ‘healthy’ aging, cognitive function is impaired in mice going along with an increased intestinal translocation of TLR ligands and alterations of TLR signaling in several brain regions.
Effect of the Mediterranean diet on the faecal long-chain fatty acid composition and intestinal barrier integrity: An exploratory analysis of the randomised controlled LIBRE trial
(2024) Seethaler, Benjamin; Basrai, Maryam; Neyrinck, Audrey M.; Vetter, Walter; Delzenne, Nathalie M.; Kiechle, Marion; Bischoff, Stephan C.
We recently showed that adherence to the Mediterranean diet increased the proportion of plasma n-3 PUFA, which was associated with an improved intestinal barrier integrity. In the present exploratory analysis, we assessed faecal fatty acids in the same cohort, aiming to investigate possible associations with intestinal barrier integrity. Women from the Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) randomised controlled trial, characterised by an impaired intestinal barrier integrity, followed either a Mediterranean diet (intervention group, n 33) or a standard diet (control group, n 35). At baseline (BL), month 3 (V1) and month 12 (V2), plasma lipopolysaccharide-binding protein, faecal zonulin and faecal fatty acids were measured. In the intervention group, faecal proportions of palmitoleic acid (16:1, n-7) and arachidonic acid (20:4, n-6) decreased, while the proportion of linoleic acid (18:2, n-6) and α linoleic acid (18:3, n-3) increased (BL-V1 and BL-V2, all P < 0·08). In the control group, faecal proportions of palmitic acid and arachidic acid increased, while the proportion of linoleic acid decreased (BL-V1, all P < 0·05). The decrease in the proportion of palmitoleic acid correlated with the decrease in plasma lipopolysaccharide-binding protein (ΔV1-BL r = 0·72, P < 0·001; ΔV2-BL r = 0·39, P < 0·05) and correlated inversely with adherence to the Mediterranean diet (Mediterranean diet score; ΔV1-BL r = –0·42, P = 0·03; ΔV2-BL r = -0·53, P = 0·005) in the intervention group. Our data show that adherence to the Mediterranean diet induces distinct changes in the faecal fatty acid composition. Furthermore, our data indicate that the faecal proportion of palmitoleic acid, but not faecal n-3 PUFA, is associated with intestinal barrier integrity in the intervention group.