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      Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review

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          Abstract

          Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut–brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

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          Most cited references109

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          Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

          An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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            Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.

            The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.
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              The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

              The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.
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                Author and article information

                Contributors
                alberto.corriero@gmail.com
                filomena.puntillo@uniba.it
                Journal
                Pain Ther
                Pain Ther
                Pain and Therapy
                Springer Healthcare (Cheshire )
                2193-8237
                2193-651X
                12 December 2023
                12 December 2023
                February 2024
                : 13
                : 1
                : 33-51
                Affiliations
                [1 ]Department of Interdisciplinary Medicine - ICU Section, University of Bari “Aldo Moro”, ( https://ror.org/027ynra39) Piazza G. Cesare 11, 70124 Bari, Italy
                [2 ]Department of Interdisciplinary Medicine - Dental Medicine Section, University of Bari “Aldo Moro”, ( https://ror.org/027ynra39) 70124 Bari, Italy
                [3 ]Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, ( https://ror.org/027ynra39) Piazza Giulio Cesare 11, 70124 Bari, Italy
                [4 ]Research, Paolo Procacci Foundation, Rome, Italy
                Author information
                http://orcid.org/0000-0001-7274-6467
                Article
                565
                10.1007/s40122-023-00565-3
                10796891
                38087070
                48e1009e-1dd6-412e-b5b5-6112207eafae
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 September 2023
                : 13 November 2023
                Categories
                Review
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                © Springer Healthcare Ltd., part of Springer Nature 2024

                cipn,chronic pain,diabetic neuropathy,faecal microbiota transplantation,microbiota,neuropathic pain,postherpetic neuralgia,probiotics,low back pain,trauma neuropathy

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