## 1 Introduction  
The human gastrointestinal tract hosts a plethora of microorganisms engaged as a functional entity. In fact, the total number of gut bacteria is estimated to be close to the total count of cells in our bodies [1]. The three domains of life, Eukarya, Bacteria, and Archaea [2], as well as their viruses, are included in the intestinal microbiome as a complex ecological community [3]. The gut microbiome has its own physiology and pathology, and increasing evidence supports its multiple functions (beneficial or detrimental) [4]. However, whereas some suggest considering the gut microbiota a \"virtual organ\" or \"emergent system\" [5, 6], many others remain cautious to describe it as such [7]. In any case, a constantly growing body of evidence is bringing us closer to understanding host-microbe species associations and the consequences of being interdependent meta-organisms [8]. The host response to xenobiotics is an important function long linked to the gut microbiome [9]. With the acknowledgment of xenobiotics sensors, such as the aryl hydrocarbon receptor (AhR), as direct mediators of the host-microbiota interplay, a greater understanding of this process has arisen [10; 11]. From its first discovery, AhR (for a long time called the \"dioxin receptor\") was related to the complex machinery involved in detoxification responses and understood as a sensor of industrial byproducts such as dioxin-like compounds (i.e., 2,3,7,8-tetrachlorobenzo-\(p\)-dioxin (TCDD), dibenzofurans, biphenyls) [12], as well as mixtures of persistent organic pollutants [13]. Indeed, the intestinal mucosa is the portal to external stimuli (e.g., toxicants, nutrients), and AhR transcriptional activity is one of the host strategies for responding to such exposures [10]. The intestinal microbiota also provides a wide range of metabolically active molecules that in many cases cannot be produced by the host. The ubiquitous AhR is capable of processing several of these chemical signals despite their structural diversity [14; 15]. However, the mechanisms underpinning such AhR-microbiota communication are complex and liable to be refined. What is clear is that some gut fermentation products such as short-chain fatty acids (SCFA) and L-tryptophan catabolites are able to activate AhR and, through this pathway, they have an important impact on human physiology and health [14; 16]. A bidirectional AhR-microbiome axis allows for the control of host intestinal homeostasis [17], and AhR activation has a fundamental role in host defense against diverse pathogenic threats [18; 19; 20]. Further, the receptor contributes to the maintenance of gut epithelial barrier integrity through the control of key pathways such as the formation of intestinal lymphoid follicles [21], which act in the regular regeneration of the colon mucosa [22]. By up-regulating the production of IL22, AhR protects intestinal stem cells from genotoxics and contributes to gut epithelial regeneration [23; 24; 25]. Thus, an intestinal deficiency of AhR is associated with an increase in gut epithelial immunopathology. Mice models have shown severe symptoms (i.e., extreme shortening of the colon, accelerated weight loss, and hemorrhages) in the absence of AhR transcriptional activity [26]. Moreover, several naturally occurring and natural-mimic ligands of AhR are chemotherapeutic suggestions for human colorectal cancer [27; 28; 29]. As a crucial gut immunomodulator, AhR is highly expressed in macrophages, dendritic cells, and T cells (e.g., FoxP3\({}^{+}\) Treg, Tr1, Th17, Th22) [16; 17; 30]. In dendritic cells, AhR participates in the expression of the enzyme indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan metabolism [31]. Furthermore, AhR activation promotes the transdifferentiation of Th17 into Tr1 [32], particularly important for regulating intestinal inflammation [33]. In systemic autoimmune disorders such as rheumatoid arthritis, the immunosuppressive function of regulatory B cells has been linked to the AhR transcriptional program [34].