Biomarkers of human gastrointestinal tract regions

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease state

Degraded Carrageenan Causing Colitis in Rats Induces TNF Secretion and ICAM-1 Upregulation in Monocytes through NF-κB Activation

Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM) and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-α expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-κB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype

Mission sur l’écosystème de la recherche et de l’innovation 14 propositions pour engager le processus de rénovation et de simplification de l’écosystème national Rapport à Madame la Ministre de l’Enseignement supérieur et de la Recherche

Mme la Ministre Sylvie Retailleau a confié à M. Philippe Gillet cette mission par lettre en date du 1er décembre 2022 (voir annexe). Après une phase de cadrage, les travaux ont été menés par l’ensemble du groupe de travail composé de Mmes Christine Cherbut et Véronique Perdereau et MM. Yves Caristan et Patrick Lévy de janvier à mai 2023. Les membres de la mission ont été appuyés par un inspecteur général de l’éducation, du sport et de la recherche, M. Charles Persoz. Cette mission s’est inscrite dans un contexte évolutif : la LPR a eu des conséquences récentes, plusieurs programmes stratégiques ont été initiés quelques mois ou quelques semaines avant le démarrage de la mission, comme les PEPR, les PUI, le programme de recherche à risque

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon

Summary Background Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. Aims To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. Methods Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0–61 wt% (IPE-0–IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using 13C-labelled IPE variants. Results In vitro, IPE-27–IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater 13C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. Conclusions IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet–gut microbiome–host metabolism axis in human

Differential effects of FODMAPs (Fermentable Oligo-, Di-, Mono-Saccharides and Polyols) on small and large intestinal contents in healthy subjects shown by MRI

OBJECTIVES: The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. METHODS: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H 2) was measured and symptoms recorded after each scan. RESULTS: Data are reported as mean (s.d.) (95 % CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0 – 5 h of SBWC to 71 (23) l / min, significantly greater than for glucose at 36 (11 – 132) l / min ( P < 0.001), whereas AUC SBWC after inulin, 33 (17 – 106) l / min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l / min ( P = 0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l / min, signifi cantly greater than glucose and glucose + fructose (both P < 0.05). Breath H 2 rose more with inulin than with fructose. Glucose when combined with fructose signifi cantly reduced breath H 2 by 7,700 (3,121 – 12,300) p.p.m. / min relative to fructose alone ( P < 0.01, n = 13). CONCLUSIONS: Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers

In vitro fermentation of juçara pulp (Euterpe edulis) by human colonic microbiota

This study was carried out to investigate the potential fermentation properties of juçara pulp, using pH-controlled anaerobic batch cultures reflective of the distal region of the human large intestine. Effects upon major groups of the microbiota were monitored over 24 h incubations by fluorescence in situ hybridisation (FISH). Short-chain fatty acids (SCFA) were measured by HPLC. Phenolic compounds, during an in vitro simulated digestion and fermentation, were also analysed. Juçara pulp can modulate the intestinal microbiota in vitro, promoting changes in the relevant microbial populations and shifts in the production of SCFA. Fermentation of juçara pulp resulted in a significant increase in numbers of bifidobacteria after a 24 h fermentation compared to a negative control. After in vitro digestion, 46% of total phenolic content still remained. This is the first study reporting the potential prebiotic effect of juçara pulp; however, human studies are necessary to prove its efficacy

Increased Oral Detection, but Decreased Intestinal Signaling for Fats in Mice Lacking Gut Microbiota

Germ-free (GF) mice lacking intestinal microbiota are significantly leaner than normal (NORM) control mice despite consuming more calories. The contribution of microbiota on the recognition and intake of fats is not known. Thus, we investigated the preference for, and acceptance of, fat emulsions in GF and NORM mice, and associated changes in lingual and intestinal fatty acid receptors, intestinal peptide content, and plasma levels of gut peptides. GF and NORM C57Bl/6J mice were given 48-h two-bottle access to water and increasing concentrations of intralipid emulsions. Gene expression of the lingual fatty acid translocase CD36 and protein expression of intestinal satiety peptides and fatty-acid receptors from isolated intestinal epithelial cells were determined. Differences in intestinal enteroendocrine cells along the length of the GI tract were quantified. Circulating plasma satiety peptides reflecting adiposity and biochemical parameters of fat metabolism were also examined. GF mice had an increased preference and intake of intralipid relative to NORM mice. This was associated with increased lingual CD36 (P<0.05) and decreased intestinal expression of fatty acid receptors GPR40 (P<0.0001), GPR41 (P<0.0001), GPR43 (P<0.05), and GPR120 (P<0.0001) and satiety peptides CCK (P<0.0001), PYY (P<0.001), and GLP-1 (P<0.001). GF mice had fewer enteroendocrine cells in the ileum (P<0.05), and more in the colon (P<0.05), relative to NORM controls. Finally, GF mice had lower levels of circulating leptin and ghrelin (P<0.001), and altered plasma lipid metabolic markers indicative of energy deficits. Increased preference and caloric intake from fats in GF mice are associated with increased oral receptors for fats coupled with broad and marked decreases in expression of intestinal satiety peptides and fatty-acid receptors

Does dietary calcium interact with dietary fiber against colorectal cancer? : a case-control study in Central Europe

BACKGROUND: An unfavorable trend of increasing rates of colorectal cancer has been observed across modern societies. In general, dietary factors are understood to be responsible for up to 70% of the disease’s incidence, though there are still many inconsistencies regarding the impact of specific dietary items. Among the dietary minerals, calcium intake may play a crucial role in the prevention. The purpose of this study was to assess the effect of intake of higher levels of dietary calcium on the risk of developing of colorectal cancer, and to evaluate dose dependent effect and to investigate possible effect modification. METHODS: A hospital based case–control study of 1556 patients (703 histologically confirmed colon and rectal incident cases and 853 hospital-based controls) was performed between 2000–2012 in Krakow, Poland. The 148-item semi-quantitative Food Frequency Questionnaire to assess dietary habits and level of nutrients intake was used. Data regarding possible covariates was also collected. RESULTS: After adjustment for age, gender, education, consumption of fruits, raw and cooked vegetables, fish, and alcohol, as well as for intake of fiber, vitamin C, dietary iron, lifetime recreational physical activity, BMI, smoking status, and taking mineral supplements, an increase in the consumption of calcium was associated with the decrease of colon cancer risk (OR = 0.93, 95% CI: 0.89-0.98 for every 100 mg Ca/day increase). Subjects consumed >1000 mg/day showed 46% decrease of colon cancer risk (OR = 0.54, 95% CI: 0.35-0.83). The effect of dietary calcium was modified by dietary fiber (p for interaction =0.015). Finally, consistent decrease of colon cancer risk was observed across increasing levels of dietary calcium and fiber intake. These relationships were not proved for rectal cancer. CONCLUSIONS: The study confirmed the effect of high doses of dietary calcium against the risk of colon cancer development. This relationship was observed across different levels of dietary fiber, and the beneficial effect of dietary calcium depended on the level of dietary fiber suggesting modification effect of calcium and fiber. Further efforts are needed to confirm this association, and also across higher levels of dietary fiber intake

International Science Foresight Workshop: Global Challenges and Research Gaps. The Royaumont process.

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