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Obesity, gut microbiota, and multiple sclerosis: Unraveling the connection.
Samara, A, Cantoni, C, Piccio, L, Cross, AH, Chahin, S
Multiple sclerosis and related disorders. 2023;:104768
Abstract
Obesity is associated with chronic mild-grade systemic inflammation and neuroinflammation. Obesity in early childhood and adolescence is also a significant risk factor for multiple sclerosis (MS) development. However, the underlying mechanisms that explain the link between obesity and MS development are not fully explored. An increasing number of studies call attention to the importance of gut microbiota as a leading environmental risk factor mediating inflammatory central nervous system demyelination, particularly in MS. Obesity and high-calorie diet are also associated with disturbances in gut microbiota. Therefore, gut microbiota alteration is a plausible connection between obesity and the increased risk of MS development. A greater understanding of this connection could provide additional therapeutic opportunities, like dietary interventions, microbiota-derived products, and exogenous antibiotics and probiotics. This review summarizes the current evidence regarding the relationships between MS, obesity, and gut microbiota. We discuss gut microbiota as a potential link between obesity and increased risk for MS. Additional experimental studies and controlled clinical trials targeting gut microbiota are warranted to unravel the possible causal relationship between obesity and increased risk of MS.
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Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults.
Demaria, M, Bertozzi, B, Veronese, N, Spelta, F, Cava, E, Tosti, V, Piccio, L, Early, DS, Fontana, L
npj aging. 2023;(1):3
Abstract
Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.
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Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer's Disease.
Rahmani, F, Ghezzi, L, Tosti, V, Liu, J, Song, SK, Wu, AT, Rajamanickam, J, Obert, KA, Benzinger, TLS, Mittendorfer, B, et al
Journal of Alzheimer's disease : JAD. 2023;(1):263-273
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Abstract
BACKGROUND Multiple sclerosis (MS) is a prototype neuroinflammatory disorder with increasingly recognized role for neurodegeneration. Most first-line treatments cannot prevent the progression of neurodegeneration and the resultant disability. Interventions can improve symptoms of MS and might provide insights into the underlying pathology. OBJECTIVE To investigate the effect of intermittent caloric restriction on neuroimaging markers of MS. METHODS We randomized ten participants with relapsing remitting MS to either a 12-week intermittent calorie restriction (iCR) diet (n = 5) or control (n = 5). Cortical thickness and volumes were measured through FreeSurfer, cortical perfusion was measured by arterial spin labeling and neuroinflammation through diffusion basis spectrum imaging. RESULTS After 12 weeks of iCR, brain volume increased in the left superior and inferior parietal gyri (p: 0.050 and 0.049, respectively) and the banks of the superior temporal sulcus (p: 0.01). Similarly in the iCR group, cortical thickness improved in the bilateral medial orbitofrontal gyri (p: 0.04 and 0.05 in right and left, respectively), the left superior temporal gyrus (p: 0.03), and the frontal pole (p: 0.008) among others. Cerebral perfusion decreased in the bilateral fusiform gyri (p: 0.047 and 0.02 in right and left, respectively) and increased in the bilateral deep anterior white matter (p: 0.03 and 0.013 in right and left, respectively). Neuroinflammation, demonstrated through hindered and restricted water fractions (HF and RF), decreased in the left optic tract (HF p: 0.02), and the right extreme capsule (RF p: 0.007 and HF p: 0.003). CONCLUSION These pilot data suggest therapeutic effects of iCR in improving cortical volume and thickness and mitigating neuroinflammation in midlife adults with MS.
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Adherence to a healthy lifestyle and multiple sclerosis: a case-control study from the UK Biobank.
Veronese, N, Yang, L, Piccio, L, Smith, L, Firth, J, Marx, W, Giannelli, G, Caruso, MG, Cisternino, AM, Notarnicola, M, et al
Nutritional neuroscience. 2022;(6):1231-1239
Abstract
BACKGROUND Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored. OBJECTIVE To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS). METHODS By using a case-control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m2) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS 728 participants with MS were matched with healthy controls (n = 2,912) using a propensity score approach. In a multivariable analysis, compared to those who scored low in the composite lifestyle score (0-1 healthy lifestyle factors), people who adopted all four low risk lifestyle factors showed a 71% lower odds of having MS (OR = 0.29; 95% CI: 0.15-0.56). Moreover, there was a strong linear trend, suggesting that the higher number of healthy lifestyle behaviors was associated with lower odds of having MS. CONCLUSION Following a healthy lifestyle is associated with a lower prevalence of MS. This association should be explored further in cohort studies.
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Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.
Cignarella, F, Cantoni, C, Ghezzi, L, Salter, A, Dorsett, Y, Chen, L, Phillips, D, Weinstock, GM, Fontana, L, Cross, AH, et al
Cell metabolism. 2018;27(6):1222-1235.e6
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Plain language summary
Calorie restriction (CR) has potent anti-inflammatory effects and has shown beneficial effects in an animal model for Multiple Sclerosis (MS). Intermittent Fasting (IF) has similar effects as CR and may be more acceptable long term than CR. This paper reports results from both an animal study and a pilot randomised controlled human clinical trial on IF and MS. The animal study showed that IF had beneficial effects on the MS animal model and that these effects were at least in part mediated by changes in the gut microbiome. 16 patients with relapsing remitting MS were enrolled during a relapse and randomised to either IF (6-7 fasting days during the two-week study) or normal eating. Changes in immune inflammatory parameters and gut flora were seen in the IF group which were similar to the beneficial changes in the animal model. The authors conclude that larger clinical studies to test IF and microbiome manipulation as a potential treatment in MS are warranted.
Abstract
Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.
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Update on multiple sclerosis, its diagnosis and treatments.
Cross, AH, Cross, KA, Piccio, L
Clinical chemistry and laboratory medicine. 2012;(7):1203-10
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Abstract
Multiple sclerosis (MS) is a central nervous system disorder, characterized by mononuclear cell inflammation, demyelination and often with extensive axonal injury. It was first described neuropathologically in the late 1800s. MS has an interesting geographical epidemiology, with a higher rate at latitudes further from the equator in both directions. Women outnumber males by about 2:1; this ratio has been increasing in recent years. Genome wide association studies have thus far identified over 50 genetic susceptibility loci, and these are rapidly expanding. Several environmental risk factors have been identified, including low serum vitamin D levels, exposure to Epstein-Barr virus and cigarette smoking. MS displays a heterogeneous disease course; most patients with the disease begin with a relapsing-remitting course, but often eventually develop steady disability progression. A small percentage of MS patients have a progressive course without clinical relapses. Several treatments are now available to decrease relapse rate and slow the accumulation of disability in patients with relapsing MS, but there is currently no effective treatment to slow the progressive forms of MS.