Biology subjects

Ribet, D.

Publications and source records attributed to Ribet, D..

10 recordsLinked to original sources

bioRxiv2026

Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa

Background: Anorexia nervosa (AN) is a typical form of eating disorder characterized by a severe body weight loss, a fear of gaining weight and dysmorphophobia. This disorder is associated with both psychiatric comorbidities and multi-organ dysfunctions. Increasing evidence suggests a role of the gut microbiota in the onset or maintenance of AN. Although a dysbiosis has been reported in patients with AN, the physiological consequences of this dysbiosis remain poorly documented. To gain further insight into the role of the gut microbiota in the pathophysiology of AN, we used the murine Activity-based Anorexia (ABA) model and compared the remodelling of the jejunal, colonic, hepatic and blood proteomes occurring in male mice with intact gut microbiota, as well as in gut microbiota-depleted animals. Results: We observed a significant proteome remodelling in several organs in response to the ABA model. More than 250 proteins involved in energy metabolism, catabolic processes, lipid metabolism, ghrelin regulation, and immune functions were found to show altered abundance in ABA mice compared to control mice. We observed in addition in the blood of ABA mice a significant increase in the level of circulating proteasome. By comparing mice treated or not with antibiotics, we identified 75 proteins whose regulation in ABA mice is gut-microbiota dependent. The other identified proteins were similarly affected in ABA mice with intact or depleted gut microbiota, suggesting that these factors are mainly regulated by food starvation and physical activity, and not directly by the gut microbiota. We finally confirmed that ORM2, a protein identified as significantly decreased in the plasma of ABA mice, is also decreased in the blood of patients suffering from AN. Conclusion: Our results demonstrate that the Activity-Based Anorexia model is associated with an extensive proteome remodelling in several organs and tissues. We highlight in addition that some of these targets are regulated in a gut microbiota-dependent manner, thereby reinforcing the hypothesis of a role of the gut microbiota in Anorexia Nervosa. Together, our study provides a valuable resource to better delineate the impact of undernutrition and maladaptive physical activity on the proteome of various organs and the role of the gut bacteria in the pathophysiology of Anorexia Nervosa.

pathology↗

bioRxiv2026

Contributions of the gut microbiota and intestinal gluconeogenesis to metabolic adaptations in a mouse model of anorexia nervosa.

Anorexia nervosa is a metabolic-psychiatric disorder characterized by severe food restriction, often accompanied by hyperactivity, associated with high mortality and the lack of specific pharmacological treatment. Despite a marked energy deficit, patients paradoxically maintain euglycemia, suggesting adaptations in energy homeostasis. This study aims to characterize the interactions between food restriction, the gut microbiota and peripheral organs in a mouse model mimicking anorexia nervosa. Our results show that food-restricted mice exhibit improved glucose tolerance and increased expression of the gluconeogenic genes G6pc and Pck1 in the intestine, suggesting an adaptation in endogenous glucose production. Gut microbiota analysis reveals a marked shift in composition in food-restricted mice, with an increase in the Lachnospiraceae and Marinifilaceae families and a decrease in Lactobacillaceae. These changes are associated with metabolic parameters such as glycemia, body weight, and GLP-1 levels. Transfer of microbiota from food-restricted mice into control mice improves glucose tolerance and increases the gluconeogenic gene expression. Furthermore, the improvement in glucose tolerance is abolished in mice lacking intestinal gluconeogenesis, suggesting that intestinal gluconeogenesis is required for the effects of the FR microbiota on glucose homeostasis. Overall, these findings highlight a complex metabolic adaptation in a mouse model of anorexia nervosa, involving interactions between the gut microbiota, intestinal gluconeogenesis and maintenance of energy homeostasis.

physiology↗

bioRxiv2026

Chronic Activity-Based Anorexia triggers a glial response in the hippocampus independent of intestinal epithelial Toll-Like Receptor 4

Anorexia nervosa is characterized by maladaptive eating behavior and cognitive dysfunction, which could be explained by a neuroinflammation. A gut dysbiosis could link gastrointestinal alterations to central dysfunctions, particularly via the toll-like receptor 4 (TLR4), which has been shown to play a key role in the activity-based anorexia (ABA) model. We aimed to evaluate the neuroinflammation and its behavioral consequences in the ABA model, and to decipher the role of the microbiota-gut-brain axis, and more specifically of TLR4, in these alterations of the central nervous system. We show that chronic restriction is more strongly associated with gut inflammation, cecal microbiota alteration and neuroinflammatory processes in the hippocampus than acute restriction. The hippocampal glial response is characterized by a loss of astrocyte density, and an increased number of deramified microglia. We further demonstrate that these alterations are independent of TLR4 expressed by intestinal epithelial cells. In conclusion, our results highlight that the chronicity of ABA-associated undernutrition alters the response of glial cells in the hippocampus that is linked with changes in microbiota composition, highlighting the importance of faster diagnosis and treatment of AN.

neuroscience↗

bioRxiv2025

Characterisation of changes in the gut microbiota associated with eating disorders

BackgroundEating disorders are serious pathologies that often begin in adolescence or young adulthood and persist for a significant period of time, with a strong negative impact on patients quality of life and mortality. The etiological origins of eating disorders are complex and involve both biological, psychological and societal factors. The gut microbiota was recently proposed as one of the potential factors involved in eating disorders. To gain a better understanding of the potential role of the gut microbiota in these diseases, we used 16S rRNA sequencing to compare the composition of the faecal microbiota of patients with all typical forms of eating disorders, i.e. anorexia nervosa, bulimia nervosa or binge-eating disorder, with that of healthy individuals. ResultsOur results demonstrate that each type of eating disorder is associated with a specific gut bacterial signature. We observed, for example, a decrease in the relative abundances of Agathobacter and Romboutsia genera and an increase in Pseudomonas in patients with anorexia, while patients with binge-eating disorder exhibit a decrease in the relative abundances of Akkermansia and Intestinimonas and an increase in Streptococcus, Eggerthella and Proteus. We also highlight a heterogeneity of gut microbiota composition in different subcategories of eating disorders, such as restricting versus binge-purge type anorexia or typical versus atypical binge-eating disorder. By focusing on the comorbidities reported by patients, we finally identified several bacterial taxa, such as Acidaminococcus and Eggerthella, whose level correlates with the occurrence of anxiety or depressive-like symptoms. ConclusionsTogether, our work demonstrates that eating disorders are associated with specific changes in gut microbiota composition and highlight the necessity to finely stratify patients to identify robust microbial signatures. In addition, we identified bacterial taxa correlating with comorbidities and decreased quality of life reported by patients. Our results now pave the way for determining the predictive value of the abundance of these taxa on the duration of the pathology or on the likelihood of relapse. They also constitute a valuable resource to further demonstrate the causal role of the gut microbiota in the onset or chronicisation of eating disorders.

microbiology↗

bioRxiv2025

Sex-dependent effects of intestinal epithelial TLR4 deletion induced before activity-based anorexia

RationaleA role for the microbiota-gut-brain axis in the pathophysiology of anorexia nervosa (AN) has emerged in the last decade. An alteration of intestinal Toll-like receptor type 4 (TLR4) has been reported in the activity-based anorexia (ABA) model with an increase in its expression at the cell surface of colonic epithelial cells. In addition, inducible TLR4 invalidation in intestinal epithelial cells (IECs) was associated with behavioral and energy balance changes in ABA mice. The aim of this study was to assess the intestinal response, e.g. inflammation, gut barrier function and gut microbiota composition, to TLR4 invalidation in IEC in ABA mice. MethodsMale and female Villin-CreERT2-TLR4 LoxP C57Bl/6 mice were injected with tamoxifen to induce a specific invalidation of TLR4 in IECs (TLR4IEC-/- mice). Then, wild-type (wt) and TLR4IEC-/- mice were subjected or not to the ABA protocol which combines an access to a running wheel and a progressively limited access to food. After 12 days, colon samples were collected and the expression of 44 mRNAs encoding proteins involved in inflammatory response, gut barrier function and homeostatic regulation was measured by qPCR. Results were compared by a two-way ANOVA (ABA x TLR4IEC-/-). Gut microbiota composition was analysed by 16S rRNA Illumina sequencing. ResultsIn both male and female ABA TLR4IEC-/- mice, the kinetics of body weight loss was slowed down. In addition, male and female ABA TLR4IEC-/- mice showed an increase and a decrease in food intake, respectively. In males, TLR4 invalidation in IEC was associated with a reduction of Tlr2, Ticam1, Myd88, Tnf, I{kappa}B, Irf3, Cxcr3 and Tgf{beta} mRNA expression and fecal calprotectin levels under control conditions but not in response to the ABA model. In females, Myd88, Il6, Cxcl1 and Ccl2 mRNA levels were increased by TLR4IEC invalidation in control mice but not in ABA, except for Ccl2. TLR4 invalidation also affected the expression of genes involved in gut barrier function in control and ABA mice in a sex-dependent manner. Male mice exhibited more marked alterations. For instance, male CT TLR4IEC-/- showed a decrease of numerous targets (Ocln, Marveld2, F11r, Tjp1, Cldn7, Cldn12, Cldn15). ABA TLR4IEC-/- mice did not exhibit this decrease but other changes were observed such as an increase in Cldn3 and Cldn7 mRNA levels. Finally, TLR4IEC invalidation in control mice, but not in ABA, altered the gut microbiota in a sex dependent manner with an increase in the abundance of Parasutterella and Desulfovibrio genera in females and males, respectively. Interestingly, the ABA model per se induced an increase in the abundance of the Lactobacillus genus in both sexes, which was not observed in ABA TLR4IEC-/-. ConclusionsOur study shows for the first time the impact of inducible TLR4 invalidation in IEC on the intestinal response. We highlighted numerous colonic alterations regarding epithelial permeability, mucosal inflammation and gut microbiota composition, in control and ABA conditions: all were partially reversed in ABA TLR4IEC-/-. TLR4 invalidation in IEC also induced changes in energy homeostasis in response to the ABA model both in female and male mice. Further studies are warranted to deeply evaluate the underlying mechanisms.

physiology↗

bioRxiv2024

In vitro activity of hydroxychloroquine in combination with antibiotics against intracellular uropathogenic Escherichia coli

BackgroundTwo pathophysiological concepts may explain recurrent UTI: a reinfection by a bacterial strain from the digestive microbiota or a relapse from Escherichia coli persisting within the superficial urothelial cells as intracellular bacterial communities (IBC). Hydroxychloroquine (HCQ)-antibiotic combination is effective against intracellular adherent-invasive E. coli isolated from patients with Crohns disease. We hypothesized that HCQ may enhanced antibiotic efficacy against E. coli IBC. MethodsUTI89 reference strain and two clinical E. coli strains forming IBCs (VITALE#2157, VITALE#2206) were used in this study. MIC, MBC and time killing curves (4xMIC) were performed for AZYTHROMYCIN (AZT), CIPROFLOXACIN (CIP), DOXYCYCLINE (DC), FOSFMOMYCIN (FF) and HCQ. In vitro activity of antibiotics alone and combined with HCQ was evaluated on intracellular bacterial survival assay using a model of urothelium cells (HTB-9). ResultsTime-killing curves showed that CIP has a bactericidal activity at H6 (-4.6 log10 CFU/mL) with regrowth at H24 against 2157, and a bactericidal activity at H6 without regrowth at H24 against 2206 (-3.3 log10 CFU/mL) and UTI89 (-3.4 log10 CFU/mL); DC, AZT and FF demonstrated bacteriostatic activity at H24 regardless of the strain. We observed a significant decrease in the number of intracellular bacteria at H42 with CIP (-1.83 log10 / 106 cells). DC, FF, and AZT exposure did not reduce IBC formation at H42 (P>0.05). IBC formation after HCQ-antibiotic combination exposure was not significantly different (P>0.05) from antibiotic exposure alone, regardless of the antibiotic or strain studied. ConclusionsIn conclusion, HCQ exposure does not enhance antibiotics activity against intracellular uropathogenic E. coli. HighlightsO_LIUsing an in vitro model of superficial urothelium monolayer, we observed a significant decrease in intracellular uropathogenic Escherichia coli in response to ciprofloxacin exposure. C_LIO_LIHydroxychloroquine exposure does not enhance antibiotics activity against intracellular uropathogenic Escherichia coli. C_LI

microbiology↗

bioRxiv2024

Gut microbiota regulates food intake in a rodent model of binge-eating disorder

ObjectiveBinge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory behaviours. This disease is a major public health issue since it decreases patients quality of life and is associated with numerous comorbidities, encompassing anxiety, depression and complications associated with obesity. The pathophysiology of binge-eating disorder is complex and involves both endogenous, environmental and sociocultural factors. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder. MethodWe used a model of binge-eating disorder where eight-weeks-old C57Bl/6 female mice had access during 2 hours, every 2 days over a 10-day period, to a highly palatable and high-calorie diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behaviour and other behavioural parameters were compared between groups. ResultsWe observed an increase in food intake in mouse exposed to high-fat high-sucrose diet, as well as tachyphagia and craving for food during binge-eating episodes. We demonstrate the gut microbiota depletion further increases food intake, specifically during binge-eating episodes. DiscussionThese results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and open the way for future therapeutic strategies aiming at targeting patients gut microbiota.

animal behavior and cognition↗

bioRxiv2024

Staphylococcus warneri dampens SUMOylation and promotes intestinal inflammation

Gut bacteria play key roles in intestinal physiology, via the secretion of diversified bacterial effectors. Many of these effectors remodel the host proteome, either by altering transcription or by regulating protein post-translational modifications. SUMOylation, a ubiquitin-like post-translational modification playing key roles in intestinal physiology, is a target of gut bacteria. Mutualistic gut bacteria can promote SUMOylation, via the production of short- or branched-chain fatty acids (SCFA/BCFA). In contrast, several pathogenic bacteria were shown to dampen SUMOylation in order to promote infection. Here, we challenge this dichotomic vision by showing that Staphylococcus warneri, a non-pathogenic bacterium of the human gut microbiota, decreases SUMOylation in intestinal cells. We identified that Warnericin RK, a hemolytic toxin secreted by S. warneri, targets key components of the host SUMOylation machinery, leading to the loss of SUMO-conjugated proteins. We further demonstrate that the dampening of SUMOylation triggered by Warnericin RK promotes inflammation, and, more particularly, TNF-dependent intestinal inflammatory responses. Together, these results highlight the diversity of mechanisms used by non-pathogenic bacteria from the gut microbiota to manipulate host SUMOylation. They further highlight that changes in gut microbiota composition may impact intestinal inflammation, by changing the equilibrium between bacterial effectors promoting or dampening SUMOylation.

microbiology↗

bioRxiv2023

Are Escherichia coli causing recurrent cystitis just ordinary Uropathogenic E. coli (UPEC) strains?

Specific determinants associated with Uropathogenic Escherichia coli (UPEC) causing recurrent cystitis are still poorly characterized. The aims of this study were (i) to describe genomic and phenotypic traits associated with recurrence using a large collection of recurrent and paired sporadic UPEC isolates, and (ii) to explore within-host genomic adaptation associated with recurrence using series of 2 to 5 sequential UPEC isolates. Whole genome comparative analyses between 24 recurrent cystitis isolates (RCIs) and 24 phylogenetically paired sporadic cystitis isolates (SCIs) suggested a lower prevalence of putative mobile genetic elements (MGE) in RCIs, such as plasmids and prophages. The intra-patient evolution of the 24 RCI series over time was characterized by SNP occurrence in genes involved in metabolism or membrane transport, and by plasmid loss in 5 out of the 24 RCI series. Genomic evolution occurred early in the course of recurrence, suggesting rapid adaptation to strong selection pressure in the urinary tract. However, RCIs did not exhibit specific virulence factor determinants and could not be distinguished from SCIs by their fitness, biofilm formation, or ability to invade HTB-9 bladder epithelial cells. Taken together, these results suggest a rapid but not convergent adaptation of RCIs that involves both strain- and host-specific characteristics. Author summaryThe recurrence of cystitis is a frequent but poorly understood phenomenon. There are currently many hypotheses trying to explain recurrence, but data on large collections of well-characterized clinical isolates are lacking. In order to identify specific recurrence-associated markers, we conducted a large genomic and phenotypic study involving 48 well-characterized cystitis isolates: 24 recurrent cystitis isolates (RCIs) and 24 pairs of isolates causing sporadic cystitis (SCIs). Moreover, we were able to explore intra-host overtime RCI evolution, by analyzing up to 5 sequential UPEC isolates per RCI series. Our results suggest that RCI rapidly adapt to their host through mobile genetic elements loss and SNP accumulation in genes involved in metabolism and membrane transport. However, no convergent genomic nor phenotypic evolution was observed between isolates collected from distinct patients. Taken together, these results suggest a host-shaped evolution of RCIs, highlighting a need for future studies focused on the host-pathogen relationships.

microbiology↗

bioRxiv2022

Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation

The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. These metabolites regulate intestinal cell activities by modulating either gene transcription or post-translational modifications of gut proteins. The effect of gut commensal bacteria on SUMOylation, an essential ubiquitin-like modification in intestinal physiology, remains however unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in different intestinal cell lines in a pH-dependent manner. We demonstrate that these metabolites induce an oxidative stress which inactivates intestinal deSUMOylases and promotes the hyperSUMOylation of chromatin-bound proteins. In order to determine the impact of these modifications on intestinal physiology, we focused on the NF-{kappa}B signaling pathway, a key player in inflammation known to be regulated by SUMOylation. We demonstrated that the hyperSUMOylation induced by SCFAs/BCFAs inhibits the activation of the NF-{kappa}B pathway in intestinal cells by blocking the degradation of the inhibitory factor I{kappa}B in response to TNF. This results in a decrease in pro-inflammatory cytokines expression, such as IL8 or CCL20, as well as a decrease in intestinal epithelial permeability in response to TNF. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses by the gut microbiota.

cell biology↗