Nathalie M. Delzenne | UCLouvain (University of Louvain) (original) (raw)

Papers by Nathalie M. Delzenne

Gut, May 5, 2016

Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD... more Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing nonalcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.

Alcoholism: Clinical and Experimental Research, 2014

Annals of Nutrition and Metabolism, 2011

Druart, C, A Neyrinck, E Dewulf, F De Backer, Sam Possemiers, Tom Van de Wiele, P Cani, Y Laronde... more Druart, C, A Neyrinck, E Dewulf, F De Backer, Sam Possemiers, Tom Van de Wiele, P Cani, Y Larondelle, and N Delzenne. 2011. “Contribution of Prebiotics-induced Changes in Gut Microbiota to Fatty Acid Composition in Adipose Tissue.” In Annals of Nutrition and Metabolism, 58:73–74. ... Druart, C, Neyrinck, A., Dewulf, E., De Backer, F., Possemiers, S., Van de Wiele, T., Cani, P., et al. (2011). Contribution of prebiotics-induced changes in gut microbiota to fatty acid composition in adipose tissue. ANNALS OF NUTRITION AND METABOLISM ( ...

Pieter Van den Abbeele UGent, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, To... more Pieter Van den Abbeele UGent, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, Tom Van de Wiele UGent, Willy Verstraete UGent, Céline Druart, F De Backer and Patrice Cani, et al. (2011) International Society of Nutrigenetics and Nutrigenomics, 5th Congress, Abstracts. ... Van den Abbeele, Pieter, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, Tom Van de Wiele, Willy Verstraete, et al. 2011. “Arabinoxylans Prevent Adverse Effects of a High Fat Diet Through Prebiotic Modulation of the Gut Microbiota.” In ...

Nature Reviews Endocrinology, Aug 9, 2011

At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and th... more At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act as an environmental factor that affects the host's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ-free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut's barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity-related disorders.

Nature Reviews Gastroenterology & Hepatology, Aug 21, 2020

Notable properties of the gut microbiota include its functionality and resilience 1. A stable gut... more Notable properties of the gut microbiota include its functionality and resilience 1. A stable gut community protects the host against invading microorganisms and helps maintain homeostasis, including immune regulation. Nonetheless, disruptions occur owing to dietary shifts, antibiotic use, age or infection, leading to a gut microbiota that can contribute to a range of inflammatory, pathogenic and metabolic conditions such as inflammatory bowel diseases, colorectal cancer, metabolic syndrome and atopy 2. Several strategies have been proposed to modulate the composition and/or function of the gut microbiota, including faecal microbiota transplants, the application of probiotics and other live microorganisms, and the use of non-digestible dietary substrates such as prebiotics 3,4. When the synbiotic concept was first described 25 years ago, the notion that selectively fermentable non-digestible food ingredients (prebiotics) could be combined with probiotics was envisioned 5. Thus, synbiotics were loosely defined as mixtures of "probiotics and prebiotics that beneficially affect the host" 5. The term itself was formed from the Greek prefix 'syn' , meaning 'together' and the suffix 'biotic' , meaning 'pertaining to life'. Despite the availability of similarly worded definitions, confusion exists among stakeholders, including scientists, about what constitutes a synbiotic 6-9. A general misunderstanding might have been, in part, because the original definition itself-that is, "mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria, thus improving host welfare"-was too wordy and lacked precision 5. In addition, the expansion of the entire '-biotics' category, including terms such as postbiotic 10 and pharmabiotic 11 , almost certainly further contributes to confusion. To provide clarity and guidance regarding appropriate use of the term 'synbiotic' , in May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened an expert panel of academic scientists

American Journal of Physiology-endocrinology and Metabolism, Apr 1, 2018

Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with chang... more Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier.

Cell Host & Microbe, Nov 1, 2013

Gut microbiota contribute to host metabolic efficiency by increasing energy availability through ... more Gut microbiota contribute to host metabolic efficiency by increasing energy availability through the fermentation of dietary fiber and production of short-chain fatty acids (SCFAs) in the colon. SCFAs are proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, which stimulates insulin secretion (incretin response) and inhibits gastric emptying. We find that germfree (GF) and antibiotic-treated mice, which have severely reduced SCFA levels, have increased basal GLP-1 levels in the plasma and increased Gcg expression in the colon. Increasing energy supply, either through colonization with polysaccharidefermenting bacteria or through diet, suppressed colonic Gcg expression in GF mice. Increased GLP-1 levels in GF mice did not improve the incretin response but instead slowed intestinal transit. Thus, microbiota regulate the basal levels of GLP-1, and increasing these levels may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption.

Alcohol and Alcoholism, Sep 1, 2015

Social Science Research Network, 2019

Patients with alcohol use disorder (AUD) present with important emotional, cognitive and social i... more Patients with alcohol use disorder (AUD) present with important emotional, cognitive and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show for the first time that the gut microbiota drives behavioral features of alcohol addiction including reduced sociability. By transplanting the gut microbiota from AUD patients to mice, we pointed out that the production of ethanol by specific bacterial genera, is associated with a lower hepatic synthesis of beta-hydroxybutyrate (BHB), and thereby prevent the protective effect of BHB on social behavior, neuroinflammation and neurotransmission. We confirmed this hypothesis detoxified AUD patients, in which we observed a persisting ethanol production in the feces as well as correlations between low plasma BHB levels and social impairments. Our data support new pathways involved in behavioral disorders associated with alcohol addiction, that could be considered for future treatments.

International Journal of Molecular Sciences

Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investiga... more Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas ...

Cells

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. ... more Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of...

Cells

Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, ... more Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-t...

intestinal health in obese patients in an human in vitro fermentation patterns G. Kalala, B.Kamba... more intestinal health in obese patients in an human in vitro fermentation patterns G. Kalala, B.Kambashi,N. Everaert, Y. Beckers, A. Richel, B. Pachikian, A.M. Neyrinck, N.M. Delzenne, J. Bindelle Université de Kinshasa, Department of Animal Production,Kinshasa-X, DR Congo, Université de Liège, Gembloux Agro-Bio Tech, B-5030, Belgium, Université catholique de Louvain, Metabolism and Nutrition, B-1200, Brussels,Belgium, Wallonie Bruxelles International, B-1080, BrusselsBelgium.

audience: researcher, professional, student, popularizationTrop fréquemment, l’expérimentation an... more audience: researcher, professional, student, popularizationTrop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle

American Journal of Physiology-Endocrinology and Metabolism, 2020

Dietary fibers are essential components of a balanced diet and have beneficial effects on metabol... more Dietary fibers are essential components of a balanced diet and have beneficial effects on metabolic functions. To gain insight into their impact on host physiology and gut microbiota, we performed a direct comparison of two specific prebiotic fibers in mice. During an 8-wk follow up, mice fed a high-fat diet (HFD) were compared with mice on a normal diet (basal condition, controls) and to mice fed the HFD but treated with one of the following prebiotics: fructooligosaccharides (FOS) or soluble corn fiber (SCF). Both prebiotic fibers led to a similar reduction of body weight and fat mass, lower inflammation and improved metabolic parameters. However, these health benefits were the result of different actions of the fibers, as SCF impacted energy excretion, whereas FOS did not. Interestingly, both fibers had very distinct gut microbial signatures with different short-chain fatty acid profiles, indicating that they do not favor the growth of the same bacterial communities. Although the...

Translational Psychiatry, 2021

The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which r... more The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine p...

Gut Microbes, 2020

Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat ... more Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.

Gastroenterology, 2020

BACKGROUND & AIMS Dysbiosis of the intestinal microbiota has been associated with nonalcoholi... more BACKGROUND & AIMS Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8±12.6 y; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subsp. lactis BB-12; n=55) or placebo (n=49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study and fecal microbiomes were analyzed by 16S rDNA sequencing. RESULTS Mean baseline and end of study magnetic resonance spectroscopy liver fat percentage values were 32.3%±24.8% and 28.5%±20.1% in the synbiotic group and 31.3%±22% and 25.2%±17.2% in the placebo group. In the unadjusted intention to treat analysis, we found no significant difference in liver fat reduction between groups (β=2.8; 95% CI, -2.2 to 7.8; P=.30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β=2; 95% CI, 1.5-2.6; P=.03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium, and reductions in Oscillibacter and Alistipes, compared with baseline; these changes were not observed in the placebo group. Changes in composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS In a randomized trial of patients with NAFLD, 1 y administration of a synbiotic combination (probiotic and prebiotic) altered fecal microbiomes but did not reduce liver fat content or markers of liver fibrosis. clinicaltrials.gov no: NCT01680640.

Gut, May 5, 2016

Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD... more Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing nonalcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.

Alcoholism: Clinical and Experimental Research, 2014

Annals of Nutrition and Metabolism, 2011

Druart, C, A Neyrinck, E Dewulf, F De Backer, Sam Possemiers, Tom Van de Wiele, P Cani, Y Laronde... more Druart, C, A Neyrinck, E Dewulf, F De Backer, Sam Possemiers, Tom Van de Wiele, P Cani, Y Larondelle, and N Delzenne. 2011. “Contribution of Prebiotics-induced Changes in Gut Microbiota to Fatty Acid Composition in Adipose Tissue.” In Annals of Nutrition and Metabolism, 58:73–74. ... Druart, C, Neyrinck, A., Dewulf, E., De Backer, F., Possemiers, S., Van de Wiele, T., Cani, P., et al. (2011). Contribution of prebiotics-induced changes in gut microbiota to fatty acid composition in adipose tissue. ANNALS OF NUTRITION AND METABOLISM ( ...

Pieter Van den Abbeele UGent, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, To... more Pieter Van den Abbeele UGent, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, Tom Van de Wiele UGent, Willy Verstraete UGent, Céline Druart, F De Backer and Patrice Cani, et al. (2011) International Society of Nutrigenetics and Nutrigenomics, 5th Congress, Abstracts. ... Van den Abbeele, Pieter, Audrey Neyrinck, Philippe Gérard, Sylvie Rabot, Aurélia Bruneau, Tom Van de Wiele, Willy Verstraete, et al. 2011. “Arabinoxylans Prevent Adverse Effects of a High Fat Diet Through Prebiotic Modulation of the Gut Microbiota.” In ...

Nature Reviews Endocrinology, Aug 9, 2011

At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and th... more At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act as an environmental factor that affects the host's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ-free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut's barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity-related disorders.

Nature Reviews Gastroenterology & Hepatology, Aug 21, 2020

Notable properties of the gut microbiota include its functionality and resilience 1. A stable gut... more Notable properties of the gut microbiota include its functionality and resilience 1. A stable gut community protects the host against invading microorganisms and helps maintain homeostasis, including immune regulation. Nonetheless, disruptions occur owing to dietary shifts, antibiotic use, age or infection, leading to a gut microbiota that can contribute to a range of inflammatory, pathogenic and metabolic conditions such as inflammatory bowel diseases, colorectal cancer, metabolic syndrome and atopy 2. Several strategies have been proposed to modulate the composition and/or function of the gut microbiota, including faecal microbiota transplants, the application of probiotics and other live microorganisms, and the use of non-digestible dietary substrates such as prebiotics 3,4. When the synbiotic concept was first described 25 years ago, the notion that selectively fermentable non-digestible food ingredients (prebiotics) could be combined with probiotics was envisioned 5. Thus, synbiotics were loosely defined as mixtures of "probiotics and prebiotics that beneficially affect the host" 5. The term itself was formed from the Greek prefix 'syn' , meaning 'together' and the suffix 'biotic' , meaning 'pertaining to life'. Despite the availability of similarly worded definitions, confusion exists among stakeholders, including scientists, about what constitutes a synbiotic 6-9. A general misunderstanding might have been, in part, because the original definition itself-that is, "mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria, thus improving host welfare"-was too wordy and lacked precision 5. In addition, the expansion of the entire '-biotics' category, including terms such as postbiotic 10 and pharmabiotic 11 , almost certainly further contributes to confusion. To provide clarity and guidance regarding appropriate use of the term 'synbiotic' , in May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened an expert panel of academic scientists

American Journal of Physiology-endocrinology and Metabolism, Apr 1, 2018

Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with chang... more Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier.

Cell Host & Microbe, Nov 1, 2013

Gut microbiota contribute to host metabolic efficiency by increasing energy availability through ... more Gut microbiota contribute to host metabolic efficiency by increasing energy availability through the fermentation of dietary fiber and production of short-chain fatty acids (SCFAs) in the colon. SCFAs are proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, which stimulates insulin secretion (incretin response) and inhibits gastric emptying. We find that germfree (GF) and antibiotic-treated mice, which have severely reduced SCFA levels, have increased basal GLP-1 levels in the plasma and increased Gcg expression in the colon. Increasing energy supply, either through colonization with polysaccharidefermenting bacteria or through diet, suppressed colonic Gcg expression in GF mice. Increased GLP-1 levels in GF mice did not improve the incretin response but instead slowed intestinal transit. Thus, microbiota regulate the basal levels of GLP-1, and increasing these levels may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption.

Alcohol and Alcoholism, Sep 1, 2015

Social Science Research Network, 2019

Patients with alcohol use disorder (AUD) present with important emotional, cognitive and social i... more Patients with alcohol use disorder (AUD) present with important emotional, cognitive and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show for the first time that the gut microbiota drives behavioral features of alcohol addiction including reduced sociability. By transplanting the gut microbiota from AUD patients to mice, we pointed out that the production of ethanol by specific bacterial genera, is associated with a lower hepatic synthesis of beta-hydroxybutyrate (BHB), and thereby prevent the protective effect of BHB on social behavior, neuroinflammation and neurotransmission. We confirmed this hypothesis detoxified AUD patients, in which we observed a persisting ethanol production in the feces as well as correlations between low plasma BHB levels and social impairments. Our data support new pathways involved in behavioral disorders associated with alcohol addiction, that could be considered for future treatments.

International Journal of Molecular Sciences

Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investiga... more Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas ...

Cells

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. ... more Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of...

Cells

Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, ... more Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-t...

intestinal health in obese patients in an human in vitro fermentation patterns G. Kalala, B.Kamba... more intestinal health in obese patients in an human in vitro fermentation patterns G. Kalala, B.Kambashi,N. Everaert, Y. Beckers, A. Richel, B. Pachikian, A.M. Neyrinck, N.M. Delzenne, J. Bindelle Université de Kinshasa, Department of Animal Production,Kinshasa-X, DR Congo, Université de Liège, Gembloux Agro-Bio Tech, B-5030, Belgium, Université catholique de Louvain, Metabolism and Nutrition, B-1200, Brussels,Belgium, Wallonie Bruxelles International, B-1080, BrusselsBelgium.

audience: researcher, professional, student, popularizationTrop fréquemment, l’expérimentation an... more audience: researcher, professional, student, popularizationTrop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle

American Journal of Physiology-Endocrinology and Metabolism, 2020

Dietary fibers are essential components of a balanced diet and have beneficial effects on metabol... more Dietary fibers are essential components of a balanced diet and have beneficial effects on metabolic functions. To gain insight into their impact on host physiology and gut microbiota, we performed a direct comparison of two specific prebiotic fibers in mice. During an 8-wk follow up, mice fed a high-fat diet (HFD) were compared with mice on a normal diet (basal condition, controls) and to mice fed the HFD but treated with one of the following prebiotics: fructooligosaccharides (FOS) or soluble corn fiber (SCF). Both prebiotic fibers led to a similar reduction of body weight and fat mass, lower inflammation and improved metabolic parameters. However, these health benefits were the result of different actions of the fibers, as SCF impacted energy excretion, whereas FOS did not. Interestingly, both fibers had very distinct gut microbial signatures with different short-chain fatty acid profiles, indicating that they do not favor the growth of the same bacterial communities. Although the...

Translational Psychiatry, 2021

The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which r... more The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine p...

Gut Microbes, 2020

Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat ... more Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.

Gastroenterology, 2020

BACKGROUND & AIMS Dysbiosis of the intestinal microbiota has been associated with nonalcoholi... more BACKGROUND & AIMS Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8±12.6 y; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subsp. lactis BB-12; n=55) or placebo (n=49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study and fecal microbiomes were analyzed by 16S rDNA sequencing. RESULTS Mean baseline and end of study magnetic resonance spectroscopy liver fat percentage values were 32.3%±24.8% and 28.5%±20.1% in the synbiotic group and 31.3%±22% and 25.2%±17.2% in the placebo group. In the unadjusted intention to treat analysis, we found no significant difference in liver fat reduction between groups (β=2.8; 95% CI, -2.2 to 7.8; P=.30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β=2; 95% CI, 1.5-2.6; P=.03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium, and reductions in Oscillibacter and Alistipes, compared with baseline; these changes were not observed in the placebo group. Changes in composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS In a randomized trial of patients with NAFLD, 1 y administration of a synbiotic combination (probiotic and prebiotic) altered fecal microbiomes but did not reduce liver fat content or markers of liver fibrosis. clinicaltrials.gov no: NCT01680640.

Bentham Science Publishers

Obesity is now classically characterized by a cluster of several metabolic disorders, and by a lo... more Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY … ), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.