## 1 Introduction  
Multiple sclerosis (MS) is an inflammatory disease that causes demyelination of the central nervous system (CNS) [1]. Worldwide, 2.8 million people are affected by MS, which is the leading cause of neurological disability in young adults [2]. Depending on the location and intensity of inflammation in the CNS, patients with MS experience a variety of symptoms, with impairment of their visual, sensory, motor, cognitive, or autonomic functions [3]. About two-thirds of patients with MS experience gastrointestinal symptoms such as constipation, dyspepsia, dysphagia, and fecal incontinence [4, 5]. While some studies suggest that these gastrointestinal symptoms derive from pathologies within the CNS--e.g., gut dysfunction might be caused by spinal cord injury [6]--other studies have shown that many patients with MS display bowel symptoms even years before a demyelinating event in the CNS [7]. The enteric nervous system (ENS) is often referred to as the little brain [8] not only because the human ENS contains between 200 and 600 million neurons [9] but also because of its unique ability to function autonomously after all connections to the CNS have been severed or even after removal of the gut from the body [10, 11]. The neurons of the ENS are organized into two major plexuses: the myenteric plexus (MP), which is located between the longitudinal and circular muscle, and the submucosal plexus (SP), which is located within the submucosal connective tissue layer [12]. Intrinsic primary afferent neurons (IPANs) detect mechanical or chemical stimuli (e.g., distinction), and communicate with motor neurons (MNs), either directly or via interneurons. The MNs of the MP affect intestinal motility [9]. Inhibitory MNs express enzymes to produce the neurotransmitters nitric oxide (NO) and vasoactive intestinal peptide (VIP), whereas in excitatory MNs, choline acetyltransferase (ChAT) synthesizes acetylcholine (ACh) [13; 14; 15; 16]. In the SP, MNs control secretion and vasodilation [17; 18] and are either cholinergic or non-cholinergic [19]. In addition, interstitial cells of Cajal (ICCs) that express the chloride channel anoctamin 1 (ANO1) are the pacemakers of the ENS [20; 21]. The number of ENS cells and their attributes, such as neurotransmitter signatures, have been shown to change as a result of many diseases of the gut, including achalasia [22] and inflammatory bowel diseases, e.g., ulcerative colitis [23; 24], and also due to aging [25; 26] and in the context of neurodegenerative disorders of the CNS such as Parkinson's disease [27; 28]. [PERSON] et al. [29] recently conducted a series of experiments in C57 BL/6J mice with experimental autoimmune encephalomyelitis (EAE), which is a common mouse model of MS. Mice were immunized with the fusion protein MP4, which consists of myelin basic protein (MBP) and the three hydrophilic domains of proteolipid protein (PLP) [30; 31]. The experiments revealed a loss of myenteric axons before neurological signs of EAE and CNS pathology as well as increased expression of glial fibrillary acidic protein (GFAP) in the ENS--a sign of gliosis [29]. In addition, a decrease in gastrointestinal transit time was reported, and ENS pathology in MP4-induced EAE was antibody-mediated [29]. [PERSON] et al. [32] used EAE induced by myelin oligodendrocyte glycoprotein (MOG\({}_{35\text{-}55}\)), proteolipid protein (PLP\({}_{139\text{-}151}\)), or spinal cord homogenate to study ENS pathology. They observed gastrointestinal dysmotiality that was accompanied by decreased GFAP levels and also suggested a B cell-dependent mechanism [32]. Interestingly, [PERSON] et al. did not observe neuronal loss in the ENS, which contrasted with the data of [PERSON] et al. Overall, these findings suggest a link between the ENS, the pathogenesis of EAE, and eventually MS. Yet, it remains unclear whether the cell types of the ENS show alterations in their numbers and phenotypes, including their neurotransmitter signature.