Planning in entropy-regularized Markov decision processes and games

International audienceWe propose SmoothCruiser, a new planning algorithm for estimating the value function in entropy-regularized Markov decision processes and two-player games, given a generative model of the environment. SmoothCruiser makes use of the smoothness of the Bellman operator promoted by the regularization to achieve problem-independent sample complexity of order O(1/ε 4) for a desired accuracy ε, whereas for non-regularized settings there are no known algorithms with guaranteed polynomial sample complexity in the worst case

Rotavirus-Like Particles: A Novel Nanocarrier for the Gut

The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP) from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP), into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells

Impact of N-Acyl-Homoserine Lactones, Quorum Sensing Molecules, on Gut Immunity

International audienceAmong numerous molecules found in the gut ecosystem, quorum sensing (QS) molecules represent an overlooked part that warrants highlighting. QS relies on the release of small molecules (auto-inducers) by bacteria that accumulate in the environment depending on bacterial cell density. These molecules not only are sensed by the microbial community but also interact with host cells and contribute to gut homeostasis. It therefore appears entirely appropriate to highlight the role of these molecules on the immune system in dysbiosis-associated inflammatory conditions where the bacterial populations are imbalanced. Here, we intent to focus on one of the most studied QS molecule family, namely, the type I auto-inducers represented by N-acyl-homoserine lactones (AHL). First described in pathogens such as Pseudomonas aeruginosa, these molecules have also been found in commensals and have been recently described within the complex microbial communities of the mammalian intestinal tract. In this mini-review, we will expound on this emergent field of research. We will first recall evidence on AHL structure, synthesis, receptors, and functions regarding interbacterial communication. Then, we will discuss their interactions with the host and particularly with agents of the innate and adaptive gut mucosa immunity. This will reveal how this new set of molecules, driven by microbial imbalance, can interact with inflammation pathways and could be a potential target in inflammatory bowel disease (IBD). The discovery of the general impact of these compounds on the detection of the bacterial quorum and on the dynamic and immune responses of eukaryotic cells opens up a new field of pathophysiology

Planning in entropy-regularized Markov decision processes and games

International audienceWe propose SmoothCruiser, a new planning algorithm for estimating the value function in entropy-regularized Markov decision processes and two-player games, given a generative model of the environment. SmoothCruiser makes use of the smoothness of the Bellman operator promoted by the regularization to achieve problem-independent sample complexity of order O(1/ε 4) for a desired accuracy ε, whereas for non-regularized settings there are no known algorithms with guaranteed polynomial sample complexity in the worst case

Planning in entropy-regularized Markov decision processes and games

International audienceWe propose SmoothCruiser, a new planning algorithm for estimating the value function in entropy-regularized Markov decision processes and two-player games, given a generative model of the environment. SmoothCruiser makes use of the smoothness of the Bellman operator promoted by the regularization to achieve problem-independent sample complexity of order O(1/ε 4) for a desired accuracy ε, whereas for non-regularized settings there are no known algorithms with guaranteed polynomial sample complexity in the worst case

Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells

International audienceBackground: Since acyl-homoserine lactone (AHL) profiling has been described in the gut of healthy subjects and patients with inflammatory bowel disease (IBD), the potential effects of these molecules on host cells have raised interest in the medical community. In particular, natural AHLs such as the 3-oxo-C12-HSL exhibit anti-inflammatory properties. Our study aimed at finding stable 3-oxo-C12-HSL-derived analogues with improved anti-inflammatory effects on epithelial and immune cells.Methods: We first studied the stability and biological properties of the natural 3-oxo-C12-HSL on eukaryotic cells and a bacterial reporter strain. We then constructed and screened a library of 22 AHL-derived molecules. Anti-inflammatory effects were assessed by cytokine release in an epithelial cell model, Caco-2, and a murine macrophage cell line, RAW264.7, (respectively, IL-8 and IL-6) upon exposure to the molecule and after appropriate stimulation (respectively, TNF-α 50 ng/mL and IFN-γ 50 ng/mL, and LPS 10 ng/mL and IFN-γ 20 U/mL).Results: We found two molecules of interest with amplified anti-inflammatory effects on mammalian cells without bacterial-activating properties in the reporter strain. The molecules furthermore showed improved stability in biological medium compared to the native 3-oxo-C12-HSL.Conclusions: We provide new bio-inspired AHL analogues with strong anti-inflammatory properties that will need further study from a therapeutic perspective

Isolates from normal human intestinal flora but not lactic acid bacteria exhibit 7α- and 7β-hydroxysteroid dehydrogenase activities

Ursodeoxycholic acid (UDCA)-producing bacteria are of clinical and industrial interest due to the multiple beneficial effects of this bile acid on human health. UDCA is the 7 b -OH epimer of the primary (i.e. synthesized by the liver) bile acid chenodeoxycholic acid (CDCA). Epimerization proceeds in two subsequent and reversible steps, catalysed by a 7 a - and a 7 b -hydroxysteroid dehydrogenase (7 a - and 7 b - HSDH), with 7oxo-lithocholic acid (7oxo-LCA) as the intermediate product. The aim of this study was to test the 7 a - and 7 b -HSDH activities of anaerobic whole cell cultures of a number of lactic acid bacteria and human intestinal isolates, using CDCA, UDCA and 7oxo- LCA as the substrates. Among 140 strains tested, 21 exhibited at least one of both 7-HSDH activities. 7 a -HSDH activity was detected in six strains, 7 b -HSDH in nine strains, and both activities in six other strains. All active strains were isolated from normal human and infant faeces. They belonged to the genera Clostridium , Eubacterium and Ruminococcus , whereas no strain of Lactobacillus , Bifidobacterium or Streptococcus was found to be active under our study conditions. The present study therefore revealed, for the first time, a number of normal human intestinal isolates supporting the epimerization of CDCA to UDCA, and further extended our knowledge of those intestinal bacteria which are responsible for 7 a -or7 b -HSDH activity. Key words: screening, bile acids, epimerization, intestinal microflora, lactic acid bacteria, probiotics

Gossip in the gut: Quorum sensing, a new player in the host-microbiota interactions

International audienceBacteria are known to communicate with each other and regulate their activities in social networks by secreting and sensing signaling molecules called autoinducers, a process known as quorum sensing (QS). This is a growing area of research in which we are expanding our understanding of how bacteria collectively modify their behavior but are also involved in the crosstalk between the host and gut microbiome. This is particularly relevant in the case of pathologies associated with dysbiosis or disorders of the intestinal ecosystem. This review will examine the different QS systems and the evidence for their presence in the intestinal ecosystem. We will also provide clues on the role of QS molecules that may exert, directly or indirectly through their bacterial gossip, an influence on intestinal epithelial barrier function, intestinal inflammation, and intestinal carcinogenesis. This review aims to provide evidence on the role of QS molecules in gut physiology and the potential shared by this new player. Better understanding the impact of intestinal bacterial social networks and ultimately developing new therapeutic strategies to control intestinal disorders remains a challenge that needs to be addressed in the future