Alterazioni età correlate del microbiota intestinale e fragilità Francesco Landi, MD, PhD Catholic University, Gemelli Hospital, Rome, Italy
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1 Alterazioni età correlate del microbiota intestinale e fragilità Francesco Landi, MD, PhD Catholic University, Gemelli Hospital, Rome, Italy
2 Aging and muscle Loss of muscle mass, strength and function
3 Aging and muscle Loss of muscle mass, strength and function
4 Aging and muscle Loss of muscle mass, strength and function
5 Aging and muscle Loss of muscle mass, strength and function
6 Under-nutrition, Sarcopenia and Frailty
7 Under-nutrition, Sarcopenia and Frailty Physical inactivity and decreased dietary intake Decreased protein synthesis and increased protein breakdown Infiltration of fat into muscle Drivers of lean body mass loss
8 Can sarcopenia/pf be prevented and/or treated????
9 PUTATIVE MECHANISMS OF PROTEIN ACTION ON MUSCLE CELLS Overview of potential pathways whereby resistance exercise and nutritional interventions may influence cellular events implicated in the regulation of muscle mass Landi F. et al. The New Metabolic Treatments For Sarcopenia Aging Clin Exp Res: 2013
10 Potential therapeutic strategies Nutrition-muscle connection The Pachinko Model Calvani R, Landi F et al. 2013
11 New perspective The mammalian holobiont The result of co-evolution of the eukaryotic and prokaryotic parts of an organism
12 Gut microbiota as a part of the gut barrier Microbiota Mucosal Barrier Epithelial barrier Endocrine system Vascular and lymphatic systems Acquired and Innate immunity Digestive enzymes
13 The gut barrier
14 The gut barrier The human gut microbiote: facts and figures The total weight of the microbiota biomass in the human gut may reach up to 1.8 kg The number of bacteria in the human gut exceeds the number of somatic cells in the body by 10-fold The gut microbiome includes 100-fold more genes than the human genome (Sommer & Bäckhed. Nat Rev Microbiol 2013;11: ; Tremaroli et al., Nature 2012;489:242 9)
15 Phylogenetic diversity of human gut microbiota Ley et al., Science, 2008, 20;320(5883):
16 Immunological dysregulation associated with dysbiosis of the Gut Microbiota Immunological equilibrium Symbionts Commensals Immunological dysequilibrium Pathobionts Pathogens with proinflammatory properties
17 The human gut microbiote and human diseases Rheumatoid arthritis Atherosclerosis Obesity Percent increase in total body 0,50 Bacterial 0,45 DNA in atherosclerotic fat after plaques Non-alcoholic steatohepatitis 0,40 0,35 Frailty in older persons 0,30 Alzheimer Disease 0,25 0,20 0,15 0,10 colonization of germ-free mice with microbiota harvested from humanised mouse donors fed a Western or a low-fat, plant polysaccharide rich diet Ab+ HC 0,05 0,00 J Exp Med 1994;180: Turnbaugh et al., Sci Transl Med Henao-Mejia Koren et et Claesson al., Nature PNAS et 2011 al., 2012 Nature. 2012;488: Firmicutes Proteobacteria Bacteriodetes
18 GMB as master Regulator of Immunity and Inflammation Activation of complement C1q Inflammation signals Receptors MUSCLE GMB metabolites and inflammation signals into systemic circulation GUT
19 Concepts on the pathophysiology of obesity and metabolic diseases related to the gut
20 The interaction between sarcopenia and diabetes Landi F et al. JAMDA, 2013
21 Factors responsible for inducing the variability in the human gut microbiota
22 Aging and variability in the human gut microbiota EUBIOSIS Modification of MICROBIOTA-HOST equilibrium during lifetime Quali-quantitative alteration of gut microbiota and its functions AGED GUT MICROBIOTA
23 Development of human gut microbiota from prenatal to elderly
24 Aging compromise the homeostatic equilibrium between microbiota and host Claesson et al, PNAS 2011
25 Aging compromise the homeostatic equilibrium between microbiota and host 367 Japanese individuals: 6 centenarians ( years old) and 7 individuals >95 years Odamaki et al. BMC Microbiology, 2016
26 Microbiota correlated with residence location (1) community-dwelling (2) attending an out-patient day hospital (3) in short-term (<6 weeks) rehabilitation hospital care (4) in long-term residential care (long-stay) Microbiota composition in elderly people living in longstay residential care facilities was different from that of the free living elderly, within the same ethno-geographic region. Long-stay microbiota had a higher proportion of phylum Bacteroidetes, compared to the proportion of phylum Firmicutes and unclassified reads in community-dwelling subjects Claesson et al, Nature 2012
27 The composition of the microbiota is determined by the composition and diversity of the diet Community Low-medium fat High fruit/fiber diet Overall Long-stay High fat Low fiber diet The most discriminating food types were vegetables, fruit and meat Claesson et al, Nature 2012
28 Ageing inevitably affects gut microbiota Candela M et al. Mech Ageing Dev 2013
29 Gut microbiota and inflammation
30 Muscle wasting: the gut microbiota as a new therapeutic target? Laure B. Bindels and Nathalie M. Delzenne The International Journal of Biochemistry & Cell Biology
31 Muscle wasting: the gut microbiota as a new therapeutic target? Laure B. Bindels and Nathalie M. Delzenne The International Journal of Biochemistry & Cell Biology
32 Possible influence of the gut microbiota on muscle physiology Protective effect of Peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1alfa) overexpression in mice towards skeletal muscle atrophy achieved through the reduction of the impact of denervation and fasting on muscle fiber diameter and on the ubiquitin-proteasome pathway activity, consequently inhibiting protein catabolism Sandri et al. Proc Natl Acad Sci USA 2006
33 Gut microbiota and protein metabolism The gut microbiota can modulate amino acids availability. Antibiotics have been shown to increase the levels of circulating amino acids, which would have been otherwise degraded by intestinal bacteria. On the other hand, the administration of specific probiotic strains such as Lactobacilli is associated with a specific faecal amino acids pattern. Furthermore, the gut microbiota exerts indirect effects on protein synthesis through the release of linoleic acid, acetate and bile salt able to reach skeletal muscle tissue and producing metabolic effects. Puiman Am J Physiol Gastrointest Liver Physiol, 2013 Torrallardona et al. J Nutr, 2003 Martin et al J Proteome Res, 2010
34 Gut microbiota and muscle
35 Understanding Longevity MUSCOLO CERVELLO INVECCHIAMENTO CON DISABILITA MECCANISMI COMUNI DI MALATTIA INVECCHIAMENTO ATTIVO Efficienza Fisica
36 Aged gut microbiota:...only deranged or a trajectory towards a different stability?
37 Factors proposed to support the gut barrier Bischoff et al. BMC Gastroenterology 2014, 14:189
38 Probiotics as New therapies? PROBIOTICS ( living organisms that can provide benefit to the Host ) PREBIOTICS ( substances that are present in the food that is not absorbed by the Host but that it is used by the gut bacteria )
39 Potential therapeutic strategies Lactobacillus Plantarum LP01: modulazione della flogosi per positivo rapporto tra citochine antinfiammatorie e proinfiammatorie Lactobacillus Buchneri LB26: probiotico inattivato che internalizza Selenio e Zinco per aumentarne la biodisponibilità Bifidobacterium Animalis specie lactis BS05: effetto antiossidante per produzione GSH e SOD Lactobacillus and Bifidobacterium are the most commonly used probiotic bacteria
40 Lactobacillus Plantarum LP01
41 Lactobacillus Buchneri LB26
42 Bifidobacterium Animalis (lactis BS05)
43 TAKE HOME MESSAGE Cell 169, , June 15, 2017
44 TAKE HOME MESSAGE
45 TAKE HOME MESSAGE The age-tailored and personalized modulation of the gut microbiota will be aimed at maintaining the microbial profile with the highest probability to help the host in preventing diseases and promoting (muscle) health Nikoletopoulou V et al. Trend in Endocrinology and Metabolism 2014
46 TAKE HOME MESSAGE
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