Dietary Polyphenols, Microbiome, and Multiple Sclerosis: From Molecular Anti-Inflammatory and Neuroprotective Mechanisms to Clinical Evidence

Abstract

Multiple sclerosis (MS) is a multifactorial, immune-mediated disease caused by complex gene-environment interactions. Dietary factors modulating the inflammatory status through the control of the metabolic and inflammatory pathways and the composition of commensal gut microbiota, are among the main environmental factors involved in the pathogenesis of MS. There is no etiological therapy for MS and the drugs currently used, often accompanied by major side effects, are represented by immunomodulatory substances capable of modifying the course of the disease. For this reason, nowadays, more attention is paid to alternative therapies with natural substances with anti-inflammatory and antioxidant effects, as adjuvants of classical therapies. Among natural substances with beneficial effects on human health, polyphenols are assuming an increasing interest due to their powerful antioxidant, anti-inflammatory, and neuroprotective effects. Beneficial properties of polyphenols on the CNS are achieved through direct effects depending on their ability to cross the blood-brain barrier and indirect effects exerted in part via interaction with the microbiota. The aim of this review is to examine the literature about the molecular mechanism underlying the protective effects of polyphenols in MS achieved by experiments conducted in vitro and in animal models of the disease. Significant data have been accumulated for resveratrol, curcumin, luteolin, quercetin, and hydroxytyrosol, and therefore we will focus on the results obtained with these polyphenols. Clinical evidence for the use of polyphenols as adjuvant therapy in MS is restricted to a smaller number of substances, mainly curcumin and epigallocatechin gallate. In the last part of the review, a clinical trial studying the effects of these polyphenols in MS patients will also be revised.

Lower Multiple Sclerosis Severity Score Is Associated with Higher Adherence to Mediterranean Diet in Subjects with Multiple Sclerosis from Northwestern Italy

“…Polyphenols have antioxidant, anti-inflammatory, and neuroprotective effects. They have the ability to cross the blood–brain barrier and exert direct effects in the central nervous system or indirect effects via interaction with the gut microbiota [ 31 ]. Interestingly, soffritto or sofrito is a common Mediterranean culinary recipe according to which onion and garlic are fried in olive oil.…”

A causal effects of gut microbiota in the development of migraine

“…The dysfunction of gut-brain axis has been investigated in some neurological disorders, including multiple sclerosis [ 49 ] and Alzheimer's disease [ 50 ]. Our study further provides a strong evidence of the role of the gut-brain axis in migraine.…”

The Roles of Caloric Restriction Mimetics in Central Nervous System Demyelination and Remyelination

“…There is also a clinical trial (NCT05740722), currently recruiting patients, that aims to evaluate the safety and efficacy of NR in the treatment of patients with progressive MS [180]. Despite the large number of in vitro and in vivo studies using animal models of MS, clinical evidence for the protective role of polyphenols in MS patients is restricted, encompassing only a few compounds, like curcumin [181]. However, taking into consideration the beneficial effects of resveratrol on mouse models of MS, as well as its established safety and its ability to modulate neuroinflammation in patients with AD, clinical trials need to be conducted to evaluate the potential of resveratrol to mitigate the symptoms of patients with MS.…”