Dataset Information

Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain.

ABSTRACT: Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor's quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development of effective treatments, as currently there are none. Observing that C57BL/6 (B6) and 129SvEv (129) mice are respectively sensitive and resistant to Paclitaxel-induced pain, we investigated the involvement of the gut microbiota in this extreme phenotypic response. Reciprocal gut microbiota transfers between B6 and 129 mice as well as antibiotic depletion causally linked gut microbes to Paclitaxel-induced pain sensitivity and resistance. Microglia proliferated in the spinal cords of Paclitaxel treated mice harboring the pain-sensitive B6 microbiota but not the pain-resistant 129 microbiota, which exhibited a notable absence of infiltrating immune cells. Paclitaxel decreased the abundance of Akkermansia muciniphila, which could compromise barrier integrity resulting in systemic exposure to bacterial metabolites and products - that acting via the gut-immune-brain axis - could result in altered brain function. Other bacterial taxa that consistently associated with both bacteria and pain as well as microglia and pain were identified, lending support to our hypothesis that microglia are causally involved in CIPN, and that gut bacteria are drivers of this phenotype.

SUBMITTER: Ramakrishna C

PROVIDER: S-EPMC6937259 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain.

Ramakrishna Chandran C Corleto Jose J Ruegger Paul M PM Logan Geoffrey D GD Peacock Beth B BB Mendonca Stacee S Yamaki Shanni S Adamson Trinka T Ermel Richard R McKemy David D Borneman James J Cantin Edouard M EM

Scientific reports 20191230 1

Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor's quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development of effective treatments, as currently there are none. Observing that C57BL/6 (B6) and 129SvEv (129) mice are respectively sensitive and resistant to Paclitaxel-induced pain, we investigated the invol ...[more]

PMID: 31889131

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Project description:Chemotherapy-induced neuropathic pain (CINP) is one of the most severe side effects of anticancer agents, such as platinum- and taxanes-derived drugs (oxaliplatin, cisplatin, carboplatin and paclitaxel). CINP may even be a factor of interruption of treatment and consequently increasing the risk of death. Besides that, it is important to take into consideration that the incidence of cancer is increasing worldwide, including colorectal, gastric, lung, cervical, ovary and breast cancers, all treated with the aforementioned drugs, justifying the concern of the medical community about the patient's quality of life. Several physiopathological mechanisms have already been described for CINP, such as changes in axonal transport, mitochondrial damage, increased ion channel activity and inflammation in the central nervous system (CNS). Another less frequent event that may occur after chemotherapy, particularly under oxaliplatin treatment, is the central neurotoxicity leading to disorders such as mental confusion, catatonia, hyporeflexia, etc. To date, no pharmacological therapy has shown satisfactory effect in these cases. In this scenario, duloxetine is the only drug currently in clinical use. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors and are present in several tissues, mainly participating in lipid and glucose metabolism and inflammatory response. There are three PPAR isoforms: ?, ?/? and ?. PPAR?, the protagonist of this review, is expressed in adipose tissue, large intestine, spleen and neutrophils. This subtype also plays important role in energy balance, lipid biosynthesis and adipogenesis. The effects of PPAR? agonists, known for their positive activity on type II diabetes mellitus, have been explored and present promising effects in the control of neuropathic pain, including CINP, and also cancer. This review focuses largely on the mechanisms involved in chemotherapy-induced neuropathy and the effects of the activation of PPAR? to treat CINP. It is the aim of this review to help understanding and developing novel CINP therapeutic strategies integrating PPAR? signalling.

Dataset Information

Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain.

Publications

Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain.

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