Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT₃ receptor antagonists and 5-HT₄ receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.

Disruption of the microbiota–gut–brain axis results in a wide range of pathologies that are affected, from the brain to the intestine. Gut hormones released by enteroendocrine cells to the gastrointestinal (GI) tract are important signaling molecules within this axis. In the search for the language that allows microbiota to communicate with the gut and the brain, serotonin seems to be the most important mediator. In recent years, serotonin has emerged as a key neurotransmitter in the gut–brain axis because it largely contributes to both GI and brain physiology. In addition, intestinal microbiota are crucial in serotonin signaling, which gives more relevance to the role of the serotonin as an important mediator in microbiota–host interactions. Despite the numerous investigations focused on the gut–brain axis and the pathologies associated, little is known regarding how serotonin can mediate in the microbiota–gut–brain axis. In this review, we will mainly discuss serotonergic system modulation by microbiota as a pathway of communication between intestinal microbes and the body on the microbiota–gut–brain axis, and we explore novel therapeutic approaches for GI diseases and mental disorders.

Serotonin (5-HT) is a key neurotransmitter synthesized both in the gut and the central nervous system. It exerts its signaling through specific receptors (5-HTR), which regulate numerous behaviors and functions such as mood, cognitive function, platelet aggregation, gastrointestinal motility, and inflammation. Serotonin activity is determined mainly by the extracellular availability of 5-HT, which is controlled by the serotonin transporter (SERT). Recent studies indicate that, by activation of innate immunity receptors, gut microbiota can modulate serotonergic signaling by SERT modulation. As part of its function, gut microbiota metabolize nutrients from diet to produce different by-products, including short-chain fatty acids (SCFAs): propionate, acetate, and butyrate. However, it is not known whether these SCFAs regulate the serotonergic system. The objective of this study was to analyze the effect of SCFAs on the gastrointestinal serotonergic system using the Caco-2/TC7 cell line that expresses SERT and several receptors constitutively. Cells were treated with different SCFAs concentrations, and SERT function and expression were evaluated. In addition, the expression of 5-HT receptors 1A, 2A, 2B, 3A, 4, and 7 was also studied. Our results show that the microbiota-derived SCFAs regulate intestinal serotonergic system, both individually and in combination, modulating the function and expression of SERT and the 5-HT1A, 5-HT2B, and 5-HT7 receptors expression. Our data highlight the role of gut microbiota in the modulation of intestinal homeostasis and suggest microbiome modulation as a potential therapeutic treatment for intestinal pathologies and neuropsychiatric disorders involving serotonin.

Given their large surface area and versatile chemical reactivity, single-walled carbon nanotubes (SWCNTs) are regarded as the basis of new pharmacological complexes. In this study, SWCNTs are chemically functionalized with fluorescein, folic acid, and capecitabine, a drug that is commonly used against colorectal cancer. These functionalized SWCNTs are dispersed in water by taking advantage of their synergistic interaction with type-II nanocrystalline cellulose (II-NCC), and the resulting colloidal system is tested in vitro on both normal (differentiated) and cancerous (proliferative) human colon cells (Caco-2). The functionalized SWCNT/II-NCC hybrids show a higher activity than the reference (capecitabine) against the Caco-2 cancer cell line. However, this effect appears to be intrinsically associated with the SWCNT/II-NCC complex, particularly boosted by fluorescein, as the presence of capecitabine is not required. In addition, confocal microscopy fluorescence imaging using cell cultures highlights the enormous potential of this nanohybrid platform for colon cancer theranostics.

GLUT8 is a facilitative glucose transporter expressed at high levels in the testis. In this study, we analyzed the GLUT8 expression in mouse testis during spermatogenesis by RT–PCR, Western blot and immunohistochemistry methods. Our results show that GLUT8 expression is limited to spermatids and spermatozoa in the testis. Expression begins when round spermatids are formed at postnatal day 24. The expression persists throughout spermiogenesis, and it is also detected in spermatozoa, but it is absent in more immature germ cells, Sertoli cells and interstitial tissue. GLUT8 immunoreactivity is always restricted to the acrosomic system in a manner that matches the acrosome system formation. The GLUT8 expression is mainly associated with the acrosomic membrane in the acrosome, although significant immunoreactivity is also found inside the acrosomic lumen. The specific GLUT8 location suggests that this transporter plays a pivotal role in the fuel supply of spermatozoa, and in the traffic of sugars during the capacitation and fertilization processes.