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Abstract

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae).

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... The metagenome sequencing of V3-4 variable regions of the bacterial 16S ribosomal RNA was carried out by the NovoGene Company (Beijing, China). Data processing and analysis were performed according to routine procedures, which have been described elsewhere in detail (8)(9)(10)(11). ...
... Over last decade, gut microbiota has attracted great scientific and public attention, and is widely recognized as the nexus of the interaction between life style (e.g., dietary habits) and health status (10). The Lachnospiraceae and Ruminococcaceae families are two most abundant and are seen as the major contributor to luminal biochemistry, while these families are also described as the health-associated core microbiome (11). Both are major SCFAs-producers in our gut and by providing nutritional energy and positional signals to the epithelial compartment play a crucial roles in maintaining the physiological homeostasis of the host. ...
... Both are major SCFAs-producers in our gut and by providing nutritional energy and positional signals to the epithelial compartment play a crucial roles in maintaining the physiological homeostasis of the host. Dysbiosis of these two families is associated with various diseases, especially obesity (15), type 2 diabetes (16), liver cirrhosis (17) and aging (11). Lachnospiraceae are significantly reduced in obesity and levels do not return to those seen in healthy controls even after gastric bypass (15), while Ruminococcaceae were seen to increased following a 2-day modified IF intervention and appear to be negatively associated with the severity of cardiometabolic disease in metabolic syndrome (18). ...
Article
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Recently we reported that in healthy volunteer Ramadan-associated intermittent fasting (RAIF) remodels the gut microbiome and resulted in an increase in small chain fatty acid producing bacteria concomitant with improved metabolic parameters. As interpretation of these results is hampered by the possible psychological effects associated with the study, we now aim to investigate RAIF in experimental animals. To this end, 6-week male BALB/c mice were subjected to RAIF (30 days of a 16-h daily fasting; n = 8) or provided with feed ad libitum ( n = 6). Fecal samples were collected before and the end of fasting and bacterial 16S rRNA sequencing was performed. We found that RAIF remodeled the composition of gut microbiota in BALB/c mice ( p < 0.01) and especially provoked upregulation of butyrate acid-producing Lachnospireceae and Ruminococcaceae ( p < 0.01), resembling the effects seen in human volunteers. Hence we conclude that the effects of RAIF on gut microbiome relate to the timing of food intake and are not likely related to psychological factors possibly at play during Ramadan.
... Beta diversity analysis showed a significant dissimilarity between both groups of long-lived subjects (CENT and NON) compared to CTLs, as previously reported [19,43,58,59]. ...
... Other strongly associated taxa in CENT were the Synergistaceae family, which belong to the Synergistetes phylum, Eggerthella, Collinsella intestinalis and Bifidobacterium bifidum (Actinobacteria), Methanobrevibacter and Methanobrevibacter smithii (Euryarchaeota phylum), as well as Rikenellaceae and Prevotella within the Bacteroidetes phylum. These associations are consistent with previous studies in which an increase in the abundance of all these taxa, with the exception of Prevotella, was observed in centenarians compared to younger subjects [19,43,58,66]. ...
... The association with the Bacteroidetes phylum was in line with previous studies [19,77,99] and disagrees with the initial hypothesis concerning the increase in the abundance of Bacteroidetes in old age, and with the reduction of the Firmicutes/Bacteroidetes ratio in older adults [6,64]. It should be borne in mind that the harmonic balance between Firmicutes and Bacteroidetes phyla in the human microbiota can be indicative of good health, but it is subject to the influence of lifestyle factors. ...
Article
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This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians' offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians' offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.
... The dynamic nature of gut microbiota diversity, composition and functionality with age (and particularly in older population) has been repeatedly demonstrated in the literature in various species, from invertebrates to humans (Clark and Walker 2018;Langille et al. 2014;O'Toole & Jeffery 2015). It is characterized by decreased alpha diversity, increased abundance of opportunistic pathogens and decreased abundance of "beneficial" species with age (Biagi et al. 2016;Biagi et al. 2010;Claesson et al. 2011;O'Toole & Jeffery 2015;O'Toole and Jeffery 2018;Salazar et al. 2017;Vaiserman, Koliada, and Marotta 2017;Woodmansey 2007;Woodmansey et al. 2004). Of note, the abundance of short chain fatty acid (SCFA) producers (Bifidobacteria, Lactobacillus spp., Faecalibacterium Prausnitzii, Akkermansia muciniphila), usually decrease with age (Biagi et al. 2016;Biagi et al. 2010;Claesson et al. 2011;O'Toole & Jeffery 2015;Salazar et al. 2017;Vaiserman, Koliada, and Marotta 2017;van Tongeren et al. 2005;Woodmansey et al. 2004). ...
... It is characterized by decreased alpha diversity, increased abundance of opportunistic pathogens and decreased abundance of "beneficial" species with age (Biagi et al. 2016;Biagi et al. 2010;Claesson et al. 2011;O'Toole & Jeffery 2015;O'Toole and Jeffery 2018;Salazar et al. 2017;Vaiserman, Koliada, and Marotta 2017;Woodmansey 2007;Woodmansey et al. 2004). Of note, the abundance of short chain fatty acid (SCFA) producers (Bifidobacteria, Lactobacillus spp., Faecalibacterium Prausnitzii, Akkermansia muciniphila), usually decrease with age (Biagi et al. 2016;Biagi et al. 2010;Claesson et al. 2011;O'Toole & Jeffery 2015;Salazar et al. 2017;Vaiserman, Koliada, and Marotta 2017;van Tongeren et al. 2005;Woodmansey et al. 2004). Along with the alteration of microbiota composition, functionality of microbial ecosystem is also subjected to a shift with an altered nutrients and xenobiotics handling capacities and metabolic pathways (Badal et al. 2020). ...
... It is clear when studying centenarians, that an interaction between microbiota composition and longevity as well as a more diverse and flexible microbiota are observed compared to elderly populations presenting health problems (Badal et al. 2020;Biagi et al. 2016;Rampelli et al. 2020). On the contrary, and even in younger population, a poor health status (chronic metabolic diseases, insulin resistance, diabetes, or inflammatory bowel disease) is associated with a decline of gut microbiota alpha diversity and/or phyla composition (Marchesi et al. 2016). ...
Article
Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.
... Clinical studies in humans shed light on the changes in gut microbiota associated with host age. Several studies highlighted a reduction in bacterial diversity in the elderly, driven by a decrease in abundant or highly prevalent core taxa in favor of rarer taxa [2,3,[22][23][24]. This agerelated dysbiosis [25,26] is further characterized by an increase in pro-inflammatory and potentially pathogenic bacteria [26], and by a detrimental lack of composition stability resulting from reduced bacterial diversity [27,28]. ...
... Thus, the increase in rare taxa relative abundance combined with higher composition turnover with age in wild macaques could suggest age-related dysbiosis. However, rare taxa may promote extreme aging [22] by replacing core members and producing important metabolites essential to a senescent organism [11]. Services provided by the gut bacterial communities may become especially critical when old subjects face inflammaging [65]. ...
... In this context, taxa with anti-inflammatory properties and producing short-chain fatty acids (SCFAs) may contribute to healthy aging [66]. As seen in humans and captive macaques [22,65,67], we found a decrease in Fusicatenibacter, Holdemanella, Roseburia, and some members of the genus Eubacterium, all known for their anti-inflammatory or SCFAs producing properties [46][47][48][49]66]. Those changes not only echo but may contribute to the increased inflammatory immune profile, or be promoted by senescent macrophages activity, observed in aging macaques [20,68]. ...
Article
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Background Pronounced heterogeneity of age trajectories has been identified as a hallmark of the gut microbiota in humans and has been explained by marked changes in lifestyle and health condition. Comparatively, age-related personalization of microbiota is understudied in natural systems limiting our comprehension of patterns observed in humans from ecological and evolutionary perspectives. Results Here, we tested age-related changes in the diversity, stability, and composition of the gut bacterial community using 16S rRNA gene sequencing with dense repeated sampling over three seasons in a cross-sectional age sample of adult female Assamese macaques ( Macaca assamensis ) living in their natural forest habitat. Gut bacterial composition exhibited a personal signature which became less stable as individuals aged. This lack of stability was not explained by differences in microbiota diversity but rather linked to an increase in the relative abundance of rare bacterial taxa. The lack of age-related changes in core taxa or convergence with age to a common state of the community hampered predicting gut bacterial composition of aged individuals. On the contrary, we found increasing personalization of the gut bacterial composition with age, indicating that composition in older individuals was increasingly divergent from the rest of the population. Reduced direct transmission of bacteria resulting from decreasing social activity may contribute to, but not be sufficient to explain, increasing personalization with age. Conclusions Together, our results challenge the assumption of a constant microbiota through adult life in a wild primate. Within the limits of this study, the fact that increasing personalization of the aging microbiota is not restricted to humans suggests the underlying process to be evolved instead of provoked only by modern lifestyle of and health care for the elderly.
... Experiments on various animal models showed that gut microbiota plays important roles in the regulation of host lifespan [4][5][6][7][8] . Clinical investigations also reveal that the gut microbial signature of centenarians is distinct from that of common elders [9][10][11][12][13] . Thus, a detailed depicting the gut microbial community in extremely aged and healthy centenarians and identifying key taxa that contribute to the longevity may provide novel strategies to achieve healthy aging. ...
... In the centenarians, the abundance of Roseburia and Escherichia was significantly higher, while Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella, and Akkermansia were significantly lower in centenarians than the non-centenarians at the genus level 1,10-12 . Currently, most metagenomic studies on longevity were based on 16S rRNA gene amplicon sequencing 12 , which cannot provide functional information. Wu et al. 13 investigated the gut microbiota structure of centenarians living at Sardinia, Italy using shotgun metagenomics method. ...
... Several studies have reported that the gut microbial structure and function of centenarians exhibit unique features as compared to ordinary adults 1,[10][11][12][13]24 . Centenarians are commonly featured by decreased alpha diversity, reduced butyrate-producing bacteria such as Faecalibacterium, Roseburia, Eubacterium and Ruminococcus, and increased opportunistic pathobionts 25 . ...
Article
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The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most microbial studies on longevity are commonly based on metagenomic sequencing which may lose information about the functional microbes with extremely low abundance. Here, we combined in-depth metagenomic sequencing and large-scale culturomics to reveal the unique gut microbial structure of a Chinese longevity population, and to explore the possible relationship between intestinal microbes and longevity. Twenty-five healthy Hainan natives were enrolled in the study, including 12 centenarians and 13 senior neighbors. An average of 51.1 Gb raw sequencing data were obtained from individual fecal sample. We assembled 1778 non-redundant metagenomic assembled genomes (MAGs), 33.46% of which cannot be classified into known species. Comparison with the ordinary people in Hainan province, the longevous cohort displayed significantly decreased abundance of butyrate-producing bacteria and largely increased proportion of Escherichia coli , Desulfovibrio piger and Methanobrevibacter smithii . These species showed a constant change with aging. We also isolated 8,030 strains from these samples by large-scale culturomics, most of which belonged to 203 known species as identified by MALDI-TOF. Surprisingly, only 42.17% of the isolated species were also detected by metagenomics, indicating obvious complementarity between these two approaches. Combination of two complement methods, in-depth metagenomic sequencing and culturomics, provides deeper insights into the longevity-related gut microbiota. The uniquely enriched gut microbes in Hainan extreme decades population may help to promote health and longevity.
... The composition of the gut microbiota of centenarians and young adults living in the same area and having similar eating habits may still be different (Biagi et al., 2016;Kong et al., 2016;Wang et al., 2019). The gut microbiota of elderly people displays greater interindividual variation than that of younger adults (Claesson et al., 2012;Nagpal et al., 2018). ...
... However, they had more heritable butyric acid-producing Cristensenellaceae as compared with young people. Similar to our study, the relative abundance of Cristensenellaceae was greater in centenarians than in young people also in Italy, China, and Korea (Biagi et al., 2016;Kong et al., 2016;Kim et al., 2019). It is noteworthy that Christensenellaceae has been associated with human longevity. ...
... These bacteria are associated with gut barrier function (tight junction) and anti-inflammatory capability (Riedel et al., 2006;Louis and Flint, 2017). The higher abundance of butyrate-producing bacteria in young people was seen also in Chinese, Korean, and Italian centenarian's studies (Biagi et al., 2010;Biagi et al., 2016;Kim et al., 2019;Wang et al., 2019;Wu et al., 2019). Butyrate reduces appetite, decreases insulin resistance, and is protective against obesity caused by a high-calorie diet (Li et al., 2018;Aoun et al., 2020). ...
Article
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The composition of centenarians’ gut microbiota has consistently been used as a model for healthy aging studies. However, there is an incomplete understanding of how childhood living conditions and eating habits affect the development and composition of gastrointestinal microbiota in centenarians with good cognitive functions. We compared the gut microbiota as well as the living and eating habits of the oldest-old group and the young people group. The richness and diversity of microbiota and the abundance of hereditary and environmental microbes were higher in people with longevity than young people. People with longevity ate more potatoes and cereal products. In their childhood, they had more exposure to farm animals and did not have sewers compared with young people. Young people’s gut microbiota contained more butyrate-producing bacteria and bacteria that characterized an animal-based Western diet. These results expand our understanding of the effects of childhood environment and diet on the development and stability of the microbiota in people with longevity.
... Not surprisingly, there is accumulating evidence that the gut microbiota also plays a significant role in longevity across species (O'Toole and Jeffery, 2015;Clark and Walker, 2018;Kim and Jazwinski, 2018;Valenzano and Seidel, 2018;Bana and Cabreiro, 2019). For example, studies using different human age cohorts identified differences in microbiota composition across various age groups (Biagi et al., 2016). Overall, several studies found that microbial diversity in the gut declines with age (Yatsunenko et al., 2012;Biagi et al., 2016;Leite et al., 2021). ...
... For example, studies using different human age cohorts identified differences in microbiota composition across various age groups (Biagi et al., 2016). Overall, several studies found that microbial diversity in the gut declines with age (Yatsunenko et al., 2012;Biagi et al., 2016;Leite et al., 2021). However, health-associated genera, such as Christensenella, Akkermansia, and Bifidobacterium, were consistently found in exceptionally long-lived individuals, like supercentenarians, suggesting their potential life span-promoting effects (Biagi et al., 2016). ...
... Overall, several studies found that microbial diversity in the gut declines with age (Yatsunenko et al., 2012;Biagi et al., 2016;Leite et al., 2021). However, health-associated genera, such as Christensenella, Akkermansia, and Bifidobacterium, were consistently found in exceptionally long-lived individuals, like supercentenarians, suggesting their potential life span-promoting effects (Biagi et al., 2016). ...
Article
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Intestinal microbial communities participate in essential aspects of host biology, including nutrient acquisition, development, immunity, and metabolism. During host aging, dramatic shifts occur in the composition, abundance, and function of the gut microbiota. Although such changes in the microbiota are conserved across species, most studies remain descriptive and at most suggest a correlation between age-related pathology and particular microbes. Therefore, the causal role of the microbiota in host aging has remained a challenging question, in part due to the complexity of the mammalian intestinal microbiota, most of which is not cultivable or genetically amenable. Here, we summarize recent studies in the fruit fly Drosophila melanogaster that have substantially progressed our understanding at the mechanistic level of how gut microbes can modulate host aging.
... Some species of Bacteroides are known for the beneficial conversion of succinate to propionate and for the production of sphingolipids that play a role in maintaining homeostasis and modulating inflammation [90,91]. As for the genus Christensenellaceae R-7 group, the family Christensenellaceae has been recently associated with health [92], and it has also been reported as a typical group found in healthy centenary subjects, thus correlating it to longevity [93]. Therefore, an increase of the abundance of this group could be extremely positive for aged people. ...
... Therefore, an increase of the abundance of this group could be extremely positive for aged people. The same publication [93] reported that Dialister and related genera are present in the gut microbiota along lifespan. This genus was particularly enhanced by the probiotic treatment in this study. ...
Article
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The decline of the immune system with aging leads elderly people to be more susceptible to infections, posing high risk for their health. Vaccination is thus important to cope with this risk, even though not always effective. As a strategy to improve protection, adjuvants are used in concomitance with vaccines, however, occasionally producing important side effects. The use of probiotics has been proposed as an alternative to adjuvants due to their efficacy in reducing the risk of common infections through the interactions with the immune system and the gut microbiota. A placebo-controlled, randomized, double-blind, clinical trial was carried out on fifty elderly subjects, vaccinated for influenza, to determine the efficacy of a probiotic mixture in reducing common infection symptoms. The incidence of symptoms was evaluated after 28 days of probiotic intake (namely, T28) and after further 28 days of follow-up (namely, T56). The number of subjects, as well as the number of days with symptoms, was remarkably reduced at T28, and even more at T56 in the probiotic group. Furthermore, the influence of probiotics on immunological parameters was investigated, showing a significant positive improvement of total antioxidant capacity and β-defensin2 levels. Finally, faecal samples collected from participants were used to assess variations in the gut microbiota composition during the study, showing that probiotic intake enhanced the presence of genera related to a healthy status. Therefore, the collected results suggested that the treatment with the selected probiotic mixture could help in reducing common infectious disease symptom incidence through the stimulation of the immune system, improving vaccine efficacy, and modulating the composition of the resident gut microbiota by enhancing beneficial genera.
... Studies have indicated that longevity is a demographic trait that involves a complex and elaborate interplay of genetic, environmental and socioeconomic variables 2,3 . Advanced age-associated markers or shifts in humans have been identified directly in the genome (FOXO3A 4 and APOE 5,6 ), within circulating metabolites (some phospholipid and sphingolipid species 7 ) and in the gut microbiota (an increased presence of Escherichia and decreased proportion of Faecalibacterium 8,9 ). However, there are questions or limitations in these association studies. ...
... Employment of LGMS on the Qidong offspring and Italian centenarians 17 , but not the latter's unrelated controls of younger ages, showed a consistent departure relative to the CMD controls (Fig. 1d). These findings provide additional evidence to corroborate the connection between gut microbiota and human longevity 9,17,19 and suggest the passing of advanced age-associated microbial composition through generations. ...
Article
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A better understanding of the biological and environmental variables that contribute to exceptional longevity has the potential to inform the treatment of geriatric diseases and help achieve healthy aging. Here, we compared the gut microbiome and blood metabolome of extremely long-lived individuals (94–105 years old) to that of their children (50–79 years old) in 116 Han Chinese families. We found extensive metagenomic and metabolomic remodeling in advanced age and observed a generational divergence in the correlations with socioeconomic factors. An analysis of quantitative trait loci revealed that genetic associations with metagenomic and metabolomic features were largely generation-specific, but we also found 131 plasma metabolic quantitative trait loci associations that were cross-generational with the genetic variants concentrated in six loci. These included associations between FADS1/2 and arachidonate, PTPA and succinylcarnitine and FLVCR1 and choline. Our characterization of the extensive metagenomic and metabolomic remodeling that occurs in people reaching extreme ages may offer new targets for aging-related interventions. The authors find extensive remodeling of the gut microbiome and blood metabolome in extremely long-lived individuals (94–105 years old) compared to their children (50–79 years old) and report distinct generation-specific and cross-generational associations with genetic and socioeconomic factors.
... Cependant, même si la génétique nous semble la cause la plus probable des La famille des Christensenellaceae a déjà été associée à un impact bénéfique pour la santé chez l'Homme et chez la souris [325]. Par exemple, elle a été associée à la longévité [326], à des impacts bénéfiques sur l'obésité [327,328] et à la santé métabolique [325]. La capacité des Christensenellaceae à produire de l'acide butyrique, un SCFA, leur confère un réel intérêt comme décrit précédemment. ...
... :[325][326][327][328][329][330][331][332][333][334] ...
Thesis
Salmonella enterica Enteritidis (SE) est l’une des principales causes d’intoxication alimentaire humaine, par le biais de la consommation de produits aviaires (viande ou œufs) contaminés. Cette bactérie est portée de manière asymptomatique par la poule, mais peut infecter et rendre malade les consommateurs de ces produits. La sélection génétique et la modulation du microbiote intestinal sont deux moyens prometteurs de diminuer son portage chez la poule et sa propagation en élevage. Les objectifs de cette thèse sont d’identifier les principaux facteurs génétiques et microbiens contrôlant le portage individuel des salmonelles dans deux modèles expérimentaux. Le modèle “poulet” a été utilisé pour l’étude de l’impact du fonds génétique sur la résistance et le microbiote caecal de jeunes individus après une infection par SE. Des analyses de la composition du microbiote et de l’expression des gènes dans les tonsilles caecales ont été menées et ont permis d’identifier des bactéries intestinales (ex. Christensenellaceae), des gènes différentiellement exprimés (ex. Fut2) et des voies de signalisation potentielles (ex. voie des acides gras à chaîne courte) associés avec la réponse à l’infection. Un impact significatif de la lignée sur la composition du microbiote a également été identifié. Le modèle “souris” a été utilisé pour l’identification de régions génomiques de l’hôte contrôlant le portage chronique de SE. Deux populations génétiques de référence, les lignées du Collaborative Cross (CC) et les souris du Diversity Outbred (DO), ont permis d’identifier de nouveaux QTls (Ses11 à Ses17) et des gènes candidats tels que Lingo2 ou Btnl4 associés à la réponse à l’infection par SE. Chez les CC, nous avons également montré une large diversité des charges bactériennes dans le foie et la rate permettant d’identifier des lignées présentant des phénotypes extrêmes à SE, sensibles (ex. CC009/Unc) ou résistantes (ex. CC024/GeniUnc), et pouvant servir de nouveaux modèles expérimentaux. Ce projet a donc permis d'identifier de nouveaux mécanismes associés à la réponse à une infection par SE, grâce à l’exploitation de deux modèles expérimentaux complémentaires.
... Network-based approaches offer methods to visualize and analyze microbial community interactions and evaluate shifts in co-occurrence, temporal dynamics, and inferred causal associations [20,[23][24][25][26]. These approaches have been used successfully with taxonomic amplicon sequencing data [27][28][29][30], which is more frequently reported, as well as metagenomic shotgun sequencing data [19,21,22,30]. While best practices for microbiome studies and their interpretation in relation to health have been recently described [2,14], concise and translationally relevant descriptions of network data remain limited. ...
... Thus, detection of modular co-occurrence patterns associated with particular conditions have been a leading area of research. Using multiple methods, modular associations of taxa have been identified as specific to body sites [20], age of participants [27] and onset of Crohn's disease [30]. Chen, et al. [22] recently employed co-occurrence detection of taxonomic and functional modules of bacteria that could robustly differentiate populations of obese patients or those with inflammatory bowel disease across multiple studies. ...
Article
Network-based approaches offer a powerful framework to evaluate microbial community organization and function as it relates to a variety of environmental processes. Emerging studies are exploring network theory as a method for data integration that is likely to be critical for the integration of ‘omics’ data using systems biology approaches. Intricacies of network theory and methodological and computational complexities in network construction, however, impede the use of these tools for translational science. We provide a perspective on the methods of network construction, interpretation and emerging uses for these techniques in understanding host–microbiota interactions.
... Clostridiales can hydrolyse proteins, lipids, and cellulosic substrates [42]. Several studies have shown that the order Clostridiales is positively associated with leanness and age [43,44]. The host sugar, as a primary energy source, may explain why Oscillospira is positively associated with leanness. ...
Article
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Understanding the developmental period or the patterns of gut microbiota is important for nutritionists when designing a feed formula or adjusting a feeding strategy. The effects of growth stage or rearing pattern on pig gut microbiota have not been fully investigated. Herein, 39 fecal samples from pigs aged 3–9 months under two rearing patterns were collected to analyze the gut microbiome. Samples were clustered into three distinct groups, namely, early (3 months), middle (5 months), and late (7 and 9 months) stages, using principal coordinate analysis and analysis of similarities test. The rearing-pattern effects were very minimal, and no differences were observed in the alpha diversity [observed operational taxonomic units (OTUs) and Shannon index] of gut microbiota. From early and middle to late stage, Shannon index gradually decreased and OTUs gradually increased. Pigs at early stage were enriched with bacteria from family Prevotellaceae, including the genera Prevotella_9 and Prevotellaceae_NK3B31, whereas pigs at late stage were enriched with family Ruminococcaceae, including genera Ruminococcaceae_UCG-005 and Oscillospira. Pigs in the semi-free-grazing farm group were significantly enriched with bacteria from order Clostridiales. Growth stage better explained the changes in porcine gut microbiota than rearing patterns.
... It was demonstrated that human microbiome can affect human health and therefore likely also longevity (Biagi et al., 2016;Dato et al., 2017;Kim et al., 2018Kim et al., , 2019Badal et al., 2020). Plant microbiome play also very important role in plant health and likely longevity via symbiotic relationships with endophytic bacteria and fungi (Basit et al., 2021;Compant et al., 2021;Ghosh et al., 2021). ...
Article
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Plants hold all records in longevity. Their aging is a complex process. In the presented review, we analyzed published data on various aspects of plant aging with focus on any inferences that could shed a light on aging in animals and help to fight it in human. Plant aging can be caused by many factors, such as telomere depletion, genomic instability, loss of proteostasis, changes in intercellular interaction, desynchronosis, autophagy, epigenetic changes and others. Plants have developed a number of mechanisms to increase lifespan. Among these mechanisms are gene duplication (“genetic backup”), the active work of telomerases, abundance of meristematic cells, capacity of maintaining the meristems permanently active and continuous activity of phytohormones. Plant aging usually occurs throughout the whole perennial life, but could be also seasonal senescence. Study of causes for seasonal aging can also help to uncover the mechanisms of plant longevity. The influence of different factors such as microbiome communities, glycation, alternative oxidase activity, mitochondrial dysfunction on plant longevity was also reviewed. Adaptive mechanisms of long-lived plants are considered. Further comparative study of the mechanisms underlying longevity of plants is necessary. This will allow us to reach a potentially new level of understanding of the aging process of plants.
... Disruption to the normal homeostasis of the gut microbiota, via antibiotic exposure for example, has been associated with a range of metabolic and immune-mediated diseases including metabolic disease, obesity and allergy (Cox and Blaser, 2015). Accumulating evidence suggests that increased diversity of the gut microbiota is associated with healthy aging in humans (Kong et al., 2016;Biagi et al., 2016). In our recent study (Lynn et al., 2021), we investigated the impact of early life antibiotic exposure on otherwise healthy, normal chow fed, wildtype mice, monitoring these mice for >700 days in comparison to untreated control mice. ...
Article
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We present this protocol using a mouse model to assess the impact of early-life antibiotic exposure on mammalian lifespan and the composition of the gut microbiota over time. We describe longitudinal fecal sampling and health monitoring following early-life antibiotic exposure. We detail DNA extraction and 16S rRNA gene sequencing to longitudinally profile the composition of the fecal microbiota. Finally, we discuss how to address potential confounders such as the stochastic recolonization of the gut microbiota following antibiotic exposure. For complete details on the use and execution of this protocol, please refer to Lynn et al. (2021).
... Moreover, A. muciniphila can restore the gut barrier at the mucous layer, facilitate lipid metabolism, reduce fat mass accumulation, and reduce the incidence of fatty liver and hypercholesterol (40). This may account for the higher distribution of A. muciniphila among semi-supercentenarians (41). In our study, patients with T1DM who received the novel probiotic product slowed down the declined rate of Akkermansia uncultured bacterium in their gut, compared with patients who received the placebo. ...
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Introduction: Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS). Research Design and Methods: A randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 daily for 6 months, and 29 patients were administered insulin therapy without extra probiotic supplement as placebo group. The variations of fasting blood glucose and HbA1c in these patients were analyzed. In addition, serum levels of inflammatory cytokines and anti-inflammatory cytokine were assessed using enzyme-linked immunosorbent assay. Patients’ stool microbiota were all subjects to NGS analysis. Results: NGS data showed elevated populations of Bifidobacterium animalis, Akkermansia muciniphila and Lactobacillus salivarius in the gut of patients with T1DM who were taking probiotics. Patients with T1DM who were administered probiotics showed significantly reduced fasting blood glucose levels compared with the before-intervention levels. The HbA1c levels of the patients also improved after administration of probiotics. The concentrations of IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced and were associated with an increased TGF-β1 expression after probiotic intervention. The persistence effect of glycemic control and immunomodulation were observed even 3 months after discontinuation of the probiotics. Conclusions: Here, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03880760.
... The exact function of the microbiome profile in accelerated aging syndromes has yet to be elucidated, although the profile has been studied in long-lived humans (Biagi et al. 2016;O'Toole and Jeffery 2015). Human progeria mice and patients have experienced intestinal dysbiosis, including increased Proteobacteria and Cyanobacteria and loss of A. muciniphila. ...
Article
Akkermansia muciniphila, a frequent colonizer in the gut mucous layer of individuals, has constantly been recognized as a promising candidate for the next generation of probiotics due to its biological advantages from in vitro and in vivo investigations. This manuscript comprehensively reviewed the features of A. muciniphila in terms of its function in host physiology and frequently utilized nutrition using the published peer-reviewed articles, which should present valuable and critical information to scientists, engineers, and even the general population. A. muciniphila is an important bacterium that shows host physiology. However, its physiological advantages in several clinical settings also have excellent potential to become a probiotic. Consequently, it can be stated that there is a coherent and direct relation between the biological activities of the gut microbiota, intestinal dysbiosis/eubiosis, and the population of A. muciniphila in the gut milieu, which is influenced by various genetical and nutritional factors. Current regulatory barriers, the need for large-scale clinical trials, and the feasibility of production must be removed before A muciniphila can be extensively used as a next-generation probiotic.
... TNF-α levels were increased in groups with the aged microbiome [138]. Furthermore, aging-associated changes in the intestinal microbiota shown to accompany aging in several species, including humans [89,[139][140][141][142], have been linked to a chronic activation of the JAK/Stat signaling cascades. It has been suggested by studies in model organisms that the inhibition of these pathways may prevent not only dysbiosis, but also age-related metaplasia [140]. ...
Article
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The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.
... There is a decrease in intestinal microbiota diversity with age and an increase in the proportion of proinflammatory pathobionts [116]. Some colon bacteria produce substances with potential geroprotective properties, for example, UroA, spermidine, vitamin K2, and short-chain fatty acids (SCFAs). ...
Article
Geroprotectors slow down aging and promote healthy longevity in model animals. Although hundreds of compounds have been shown to extend the life of laboratory model organisms, clinical studies on potential geroprotectors are exceedingly rare, especially in healthy elders. This review aims to classify potential geroprotectors based on the mechanisms by which they influence aging. These pharmacological interventions can be classified into the following groups: those that prevent oxidation; proteostasis regulators; suppressors of genomic instability; epigenetic drugs; those that preserve mitochondrial function; inhibitors of aging-associated signaling pathways; hormetins; senolytics/senostatics; anti-inflammatory drugs; antifibrotic agents; neurotrophic factors; factors preventing the impairment of barrier function; immunomodulators; and prebiotics, metabiotics, and enterosorbents.
... The colonization of Akkermansia in the gut was reported to relieve appendicitis-related inflammation and inflammatory bowel disease [34]. A recent clinical study discovered that Akkermansia were significantly increased among semisupercentenarians (age 105-109 years), which suggests that Akkermansia might play a part in building new gut homeostasis in extreme aging people [35]. ...
Article
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Aging is an irreversible physiological degradation of living organisms. Accumulated oxidative stress and dysbiosis accelerate aging. Probiotics such as Lactobacillus and Bifidobacterium and their fermented metabolites (postbiotics) have been discovered to exhibit antioxidative activities that regulate oxidative stress and protect cells from oxidative damage. We screened selected Lactobacillus and Bifidobacterium strains and their postbiotics for potential antioxidative activity by using DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Strains with their metabolites were selected for mixed formula in experiments involving aging mice. The aged groups presented higher oxidative stress in the brain, liver, heart, and kidney than did young mice. However, treatment with probiotic strains and their postbiotics elevated antioxidative levels, especially in the high-dose probiotics plus postbiotics group. Next-generation sequencing data revealed positive microbiota alterations of Lactobacillus and Bifidobacterium and Akkermansia in the gut. Lactobacillus johnsonii and Akkermansia muciniphila exhibited effective enlargement of relative abundance. Besides, high-dose probiotics and high-dose probiotics plus postbiotics showed significant elevation in serum SCFAs, especially in butyrate. In conclusion, the formula containing Bifidobacterium animalis subsp. infantis BLI-02, Bifidobacterium breve Bv889, Bifidobacterium bifidum VDD088, B. animalis subsp. lactis CP-9, and Lactobacillus plantarum PL-02 and their metabolites may benefit aged people’s health.
... A study by Biagi et [12]. Typical beneficial bacteria, which are indicators of healthy aging, identified in Italian centenarians (99-104 years old) and semi-supercentenarians (105-109 years old) decreased during aging [57]. These included the Ruminococcaceae, Lachnospiraceae, and Bacteridaceae families. ...
Article
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Aging is typically accompanied by biological and physiological changes that alter cellular functions. Two of the most predominant phenomena in aging include chronic low-grade inflammation (inflammaging) and changes in the gut microbiota composition (dysbiosis). Although a direct causal relationship has not been established, many studies have reported significant reductions in inflammation during aging through well-maintained gut health and microbial balance. Prebiotics and probiotics are known to support gut health and can be easily incorporated into the daily diet. Unfortunately, few studies specifically focus on their significance in reducing inflammation during aging. Therefore, this review summarizes the scientific evidence of the potential roles of probiotics and two types of prebiotics, resistant starch and resistant proteins, in later age. Studies have demonstrated that the oral consumption of bacteria that may contribute to anti-inflammatory response, such as Bifidobacterium spp., Akkermansia munichipilla, and Faecalis praunitzii, contributes significantly to the suppression of pro-inflammatory markers in elderly humans and aged animals. Colonic fermentation of resistant starch and proteins also demonstrates anti-inflammatory activity owing to the production of butyrate and an improvement in the gut microbiota composition. Collectively, probiotics, resistant starch, and resistant proteins have the potential to promote healthy aging.
... Within three independent cohorts, comprising 9,000 individuals, researchers identified a pattern of healthy aging characterized by a depletion of core gut microbial taxa, namely Bacteroides, with healthier individuals having increasingly distinct microbiome compositions compared to other members within the study (Lau et al., 2021;Wilmanski et al., 2021). Another study, examining the microbiome compositions of "semisupercentenarians, " individuals aged 105-109 years, found that aging is marked by increasing abundance of subdominant species, with decreases in dominant core microbiota within the Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families (Biagi et al., 2016). Semi-supercentenarians showed peculiarities in their microbiome compositions, indicating enrichment of health-associated bacterial groups such as Akkermansia and Bifidobacterium, which contributed to the maintenance of good health during aging. ...
Article
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Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.
... Previous studies have shown that Ruminococcaceae can produce SCFAs and maintain a healthy gastrointestinal tract (McNabney and Henagan, 2017;Videvall et al., 2020). In addition, Ruminococcaceae is reduced in older people and aged monkeys (Biagi et al., 2016;Duan et al., 2019). Therefore, we conclude that PDX treatment can modulate the gut microbiota in obese mice and significantly increase several beneficial microbes, including Bacteroides, Parabacteroides, Alloprevotella, Muribaculum, Akkermansia, Ruminococcaceae_UCG-014, and UBA 1819. ...
Article
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The soluble dietary fiber polydextrose (PDX) is a randomly linked glucose oligomer containing small amounts of sorbitol and citric acid and is widely used in the food industry. However, whether PDX can prevent and treat obesity in high-fat diet (HFD)-fed mice has not been directly investigated, and further studies are needed to better understand the complex interactions among PDX, adipose tissue inflammation and the gut microbiota. In the present study, PDX reduced body weight, fasting blood glucose (FBG), adipose tissue accumulation, adipocyte hypertrophy, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels in HFD-fed mice. Moreover, PDX alleviated serum lipopolysaccharide (LPS) levels and macrophage infiltration in epididymal adipose tissue and resulted in macrophage polarization toward the M2 phenotype. Gut microbiota analysis revealed that PDX promoted the growth of beneficial microbes such as Bacteroides , Parabacteroides , Alloprevotella , Muribaculum , Akkermansia , Ruminococcaceae_UCG-014 and UBA1819 in obese mice, which were negatively correlated with subcutaneous fat, epididymal fat, body weight, FBG, serum TC, HDL-C, LDL-C and LPS levels. Our results indicates that PDX can prevent and treat obesity in HFD-fed mice, specifically in alleviating glucolipid metabolism disorders and adipose tissue inflammation, which may be mediated by modulating the structure of the gut microbiota. Therefore, PDX may become a promising nondrug therapy for obesity.
... We observed that the Christensenellaceae family was more abundant in low Salmonella carriers (Figs. 6 and 7). This bacteria family is associated with a beneficial impact on health in humans and in mice [56][57][58][59]. Interestingly, it has been shown that Christensenellaceae is one of the most heritable bacterial families of the human intestinal microbiota [56]. ...
Article
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Background Salmonella Enteritidis (SE) is one of the major causes of human foodborne intoxication resulting from consumption of contaminated poultry products. Genetic selection of animals that are more resistant to Salmonella carriage and modulation of the gut microbiota are two promising ways to decrease individual Salmonella carriage. The aims of this study were to identify the main genetic and microbial factors that control the level of Salmonella carriage in chickens ( Gallus gallus ) under controlled experimental conditions. Two-hundred and forty animals from the White Leghorn inbred lines N and 6 1 were infected by SE at 7 days of age. After infection, animals were kept in isolators to reduce recontamination of birds by Salmonella . Caecal contents were sampled at 12 days post-infection and used for DNA extraction. Microbiota DNA was used to measure individual counts of SE by digital PCR and to determine the bacterial taxonomic composition, using a 16S rRNA gene high-throughput sequencing approach. Results Our results confirmed that the N line is more resistant to Salmonella carriage than the 6 1 line, and that intra-line variability is higher for the 6 1 line. Furthermore, the 16S analysis showed strong significant differences in microbiota taxonomic composition between the two lines. Among the 617 operational taxonomic units (OTU) observed, more than 390 were differentially abundant between the two lines. Furthermore, within the 6 1 line, we found a difference in the microbiota taxonomic composition between the high and low Salmonella carriers, with 39 differentially abundant OTU. Using metagenome functional prediction based on 16S data, several metabolic pathways that are potentially associated to microbiota taxonomic differences (e.g. short chain fatty acids pathways) were identified between high and low carriers. Conclusions Overall, our findings demonstrate that the caecal microbiota composition differs between genetic lines of chickens. This could be one of the reasons why the investigated lines differed in Salmonella carriage levels under experimental infection conditions.
... Indeed, these differences are also seen in aged individuals and centenarians from different parts of the world. For example, centenarians in an Italian cohort had a microbiome specifically enriched in Akkermansia, Bifidobacterium, and Christensenella [34], compared to centenarians in the Chinese Hainan Centenarian Cohort Study, which was dominated by Bacteroides and Escherichia [138] (reviewed in detail [83]). With increasing awareness of the differences between populations, more studies involving diverse ethnicities and regions have been conducted, but there still are remaining uncertainties. ...
Article
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The term 'old age' generally refers to a period characterized by profound changes in human physiological functions and susceptibility to disease that accompanies the final years of a person's life. Despite the conventional definition of old age as exceeding the age of 65 years old, quantifying aging as a function of life years does not necessarily reflect how the human body ages. In contrast, characterizing biological (or physiological) aging based on functional parameters may better reflect a person's temporal physiological status and associated disease susceptibility state. As such, differentiating 'chronological aging' from 'biological aging' holds the key to identifying individuals featuring accelerated aging processes despite having a young chronological age and stratifying them to tailored surveillance, diagnosis, prevention, and treatment. Emerging evidence suggests that the gut microbiome changes along with physiological aging and may play a pivotal role in a variety of age-related diseases, in a manner that does not necessarily correlate with chronological age. Harnessing of individualized gut microbiome data and integration of host and microbiome parameters using artificial intelligence and machine learning pipelines may enable us to more accurately define aging clocks. Such holobiont-based estimates of a person's physiological age may facilitate prediction of age-related physiological status and risk of development of age-associated diseases.
... Whereas harmful pathobionts like Proteobacteria were a minority. These microbial changes had probably helped them escape from major age-related diseases and achieve an overall good health (Biagi et al., 2016). Thus, targeting age-related gut dysbiosis could emerge as an effective therapeutic strategy to maintain a balanced immune response during ageing and protect against several age-related diseases. ...
Article
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Human beings and their indigenous microbial communities have coexisted for centuries, which led to the development of co-evolutionary mechanisms of communication and cooperation. Such communication machineries are governed by sophisticated multi-step feedback loops, which typically begin with the recognition of microbes by pattern recognition receptors (PRRs), followed by a host transcriptional response leading to the release of effector molecules. Our gastrointestinal tract being the main platform for this interaction, a variety of host intestinal cells tightly regulate these loops to establish tolerance towards the microbial communities of the gut and maintain homeostasis. The transcription factor, nuclear factor kappa B (NF-κB) is an integral component of such a communication apparatus, which plays a critical role in determining the state of homeostasis or inflammation associated with dysbiosis in the host. Here we outline the crucial role of NF-κB in host response to microbial cues in the context of ageing and associated diseases.
... Lachnospiraceae members are short-chain fatty acid propionate producers and microbiota composition modulator in gut [32]. Unclassified Lachnospiraceae members enrich in the gut microbiota of centenarians in China and Italy [33,34]. Therefore, the increase in unclassified Lachnospiraceae could be a signature of positive effects tea treatment provided, which turned the high-fat diet microbiome towards a healthy and longevity microbiome [35]. ...
Article
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High-fat diet (HFD) may induce changes of metabolism and gut microbiota changes, and these changes are susceptible to diet adjustments such as tea treatment. However, the treatment effects may vary among different types of tea. In this study, we evaluated the effects of six types of tea on glucose and lipid metabolism and gut microbiota in HFD mice. We established HFD mouse model by 12 weeks feed with 60% fat diet, then treated with teas for six weeks. Here, we showed that treatment with different types of tea can inhibit weight gain and insulin resistance though different ways. Green tea regulated lipid metabolism by regulating the expression of adenosine 5′-monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase-I (CPT-1). The effect of dark tea and white tea in reducing liver weight seemed to be related to activities of acetyl-CoA carboxylase (ACC). Yellow tea exhibited the best anti-inflammatory and antioxidant effects and effects of recovering the disorder of model mouse microbiota. The decrease in blood sugar and the upregulation of gluconeogenesis-related enzymes seemed to be related to the decrement of unclassified Lachnospiraceae. These different effects may result from the unique chemical compositions contained by different types of tea, which can regulate different lipid and glucose metabolism-related proteins. Despite variations in its compositions and metabolic reactions, tea is a potent antiobesity and hypoglycemic agent.
... There is evidence that innate immunity is stimulated when food is ingested, starting "postprandial inflammation" that is part of the response to meals, as inflammatory markers increase after ingestion of food through several molecular mechanisms [139,140]. The gut microbiota represents the boundary between diet, the host metabolism, and the innate immune response [141] and may also undergo profound remodeling with aging [142][143][144][145]. Its composition depends on several factors such as individual-based (age, gender, genetics, lifestyle, method of childbirth, and whether one was breastfed or formula fed), population-based (ethnicity, cultural habits, nutrition, population genetic structure, and ancestry), and environmentbased (climate, use of antibiotics, and lifelong immunological stimuli) factors, constituting a sort of biography of each person [146]. ...
Article
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Osteoarthritis is a highly prevalent disease particularly in subjects over 65 years of age worldwide. While in the past it was considered a mere consequence of cartilage degradation leading to anatomical and functional joint impairment, in recent decades, there has been a more dynamic view with the synovium, the cartilage, and the subchondral bone producing inflammatory mediators which ultimately lead to cartilage damage. Inflammaging is defined as a chronic, sterile, low-grade inflammation state driven by endogenous signals in the absence of infections, occurring with aging. This chronic status is linked to the production of reactive oxygen species and molecules involved in the development of age-related disease such as cancer, diabetes, and cardiovascular and neurodegenerative diseases. Inflammaging contributes to osteoarthritis development where both the innate and the adaptive immune response are involved. Elevated systemic and local inflammatory cytokines and senescent molecules promote cartilage degradation, and antigens derived from damaged joints further trigger inflammation through inflammasome activation. B and T lymphocyte populations also change with inflammaging and OA, with reduced regulatory functions, thus implicating self-reactivity as an additional mechanism of joint damage. The discovery of the underlying pathogenic pathways may help to identify potential therapeutic targets for the management or the prevention of osteoarthritis. We will provide a comprehensive evaluation of the current literature on the role of inflammaging in osteoarthritis and discuss the emerging therapeutic strategies.
... Aging is also associated with reduction in bacterial diversity, unusual phylum proportions and decline in health promoting bacteria species [60,61]. Specifically, the aging microbiota has been characterized by a reduction in the Firmicutus:Bacteroidetes ratio [62,63] and by overpopulation of facultative anaerobes [64]. In conventionally housed mice, microbial dysbiosis, intestinal permeability, and circulating bacterial products increase with age, whereas these changes are not observed in germ-free mice, which live longer [65]. ...
Article
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The gut microbiota has recently gained attention due to its association with cardiovascular health, cancers, gastrointestinal disorders, and non-communicable diseases. One critical question is how the composition of the microbiota contributes to cardiovascular diseases (CVDs). Insightful reviews on the gut microbiota, its metabolites and the mechanisms that underlie its contribution to CVD are limited. Hence, the aim of this review was to describe linkages between the composition of the microbiota and CVD, CVD risk factors such as hypertension, diet, ageing, and sex differences. We have also highlighted potential therapies for improving the composition of the gut microbiota, which may result in better cardiovascular health.
... Although Akkermansia levels showed a positive trend, the study did not achieve significant changes in body weight, fat mass, or hip and waist circumference (11). While very promising, it reinforces work previously published that confirms A. muciniphila's modulation and effect are likely mediated by multiple and potentially confounding factors, including variations in diet (macronutrients as well as calories), nutritional status, host health, lumen environment, ethnicity, gender, age, medication use, mucin structure, and availability, as well as baseline abundance of Akkermansia and other organisms (12,30,(50)(51)(52)(53)(54)(55)(56)(57)(58). These confounding factors, which contribute to modulating Akkermansia, may offer further explanation for many of the conflicting data noted in previous publications. ...
Article
The effect of the novel IQP-AE-103 (proprietary combination of dehydrated okra powder and inulin) on body weight reduction and the association with changes in microbiota composition were investigated in a double-blind, randomized, placebo-controlled trial. A total of seventy-two overweight or moderately obese subjects with a body mass index of ≥25 and <35 kg/m2 were randomly allocated to receive IQP-AE-103 or placebo; each group received two IQP-AE-103 or placebo capsules three times daily, respectively. Body weight, body fat, waist circumference, and hip circumference were measured, and fecal samples were collected at baseline and after 12 weeks of intervention. Using 16S rRNA gene sequencing on the fecal samples, the microbiota dissimilarity, diversity, and differences in relative abundance between or within groups were analyzed. At the end of the study, body weight was significantly reduced in the IQP-AE-103 group compared with the placebo group, 5.16 ± 2.39 kg vs. 0.97 ± 2.09 kg (p < 0.001). Subjects from the IQP-AE-103 group who achieved a reduction of ≥5% of total body weight from baseline (hereafter referred to as 5% responders or IQP5) had a mean body weight reduction of 6.74 ± 1.94 kg, significantly greater than the placebo group (p < 0.001). Using Lefse and statistical analysis, subjects in the IQP-AE-103 group had a significantly lower relative abundance of Firmicutes than the placebo group (p < 0.05) after 12 weeks of intervention. The 5% responders from the IQP-AE-103 group had a remarkable 4.6-fold higher relative abundance of Akkermansia muciniphila than the placebo group (p < 0.05). As the significant differences between groups were only observed post-intervention, the overall differences in microbiota profile suggest that the weight loss in overweight and moderately obese subjects who consumed IQP-AE-103 for 12 weeks is accompanied by a positive change in microbiota composition. These changes might be linked to the beneficial effects of microbiome modulations in alleviating obesity and metabolic syndrome. To the best of our knowledge, we are the first to report over-the-counter (OTC) supplementation that results in both significant changes in weight and favorable shifts on the subject microbiota profile. The trial is registered under ClinicalTrials.gov Identifier no. NCT03058367.
... Several independent studies using 16S sequencing and metagenomics analysis demonstrate that the gut microbiota structure undergoes significant transformation during aging. For example, in a study that investigated the gut microbiota composition of semi-supercentenarians (!105 years old) and compared it to adult (22-48 years old), elderly (65-75 years old), and centenarian (99-104 years old) microbiota, it was found that longevity is linked to changes in the microbial ecosystem with enrichment of certain taxa [115]. ...
Article
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Recent research has been uncovering the role of the gut microbiota for brain health and disease. These studies highlight the role of gut microbiota on regulating brain function and behavior through immune, metabolic, and neuronal pathways. In this review we provide an overview of the gut microbiota axis pathways to lay the groundwork for upcoming sessions on the links between the gut microbiota and neurogenerative disorders. We also discuss how the gut microbiota may act as an intermediate factor between the host and the environment to mediate disease onset and neuropathology. Based on the current literature, we further examine the potential for different microbiota-based therapeutic strategies to prevent, to modify, or to halt the progress of neurodegeneration.
... Secondly, although bacteria in a planktonic state are not generally regarded as direct causal agents of oral diseases, saliva is a major vector for the intraoral transmission of pathogenic bacteria [24,25]. It is known that the composition of the intraoral microbiome changes with age [26], and research into the gut microbiome has proposed possible determinants of healthy aging with a special health-related composition [27,28]. It is therefore, possible that these factors may equally play a role in the oral cavity and in retaining one's natural teeth for 100 years or more. ...
Article
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Aim: To investigate associations between oral health-related conditions and the oral microbiome in a representative study sample of centenarians. Materials and methods: Clinical and microbial parameters from 54 centenarians were assessed in the Heidelberg Dental Centenarian Study. Plaque and salivary samples were collected, and the microbiota was characterized by 16S rRNA gene sequencing. Results: Diversity and structure of the oral microbiome were mainly influenced by the presence of natural teeth and the number of decayed, missing, and filled teeth (0.028 ≤ p ≤ 0.001 in plaque and salivary samples). Centenarians with less caries experience possessed a more diverse oral microbiome. Moreover, the number of dental visits also showed a significant influence on the microbial composition. Most centenarians presented with hyposalivation (mean stimulated flow rate = 0.84 ± 0.55 ml/min), a low buffering capacity, and an acidic pH. The latter was between 5.0 and 5.8 in 46.3% of cases, and we observed that an increased salivary pH correlated with higher alpha-diversity in both salivary and plaque samples. Conclusion: The microbiome diversity correlated significantly with successful oral aging. In addition, regular dental visits were a beneficial factor. However, diversity can be negatively influenced by hyposalivation, associated with pH changes due to aging effects.
Article
Aging and inflammation both contribute pivotally to cardiovascular (CV) and cerebrovascular disease, the leading causes of death and disability worldwide. The concept of inflamm-aging recognizes that low-grade inflammatory pathways observed in the elderly contribute to CV risk. Understanding the mechanisms that link inflammation and aging could reveal new therapeutic targets and offer options to cope with the growing aging population worldwide. This review reports recent scientific advances in the pathways through which inflamm-aging mediates age-dependent decline in CV function and disease onset and considers critically the translational potential of such concepts into everyday clinical practice.
Article
The gut microbiota is implicated in diverse interactions affecting human health. The present study reports a randomized, double-blind, placebo-controlled clinical study conducted by administering a new synbiotic formulation composed of two Lactobacillus strains (L. plantarum and L. acidophilus) and one Bifidobacterium strain (B. animalis subsp. lactis) and two types of fructans (fructo-oligosaccharides with a degree of polymerization of 3–5 and inulin-type fructans with 10 DP). The effects of this synbiotic were evaluated on healthy subjects for 28 days and the maintenance of its efficacy was evaluated at the end of a follow-up period of 28 days. The synbiotic treatment contributes to higher biodiversity of the gut microbiota, increasing the community richness with respect to the group with the prebiotics alone and the placebo group. Its positive effect is also reflected in the variation of microbial community structure favoring the beneficial short-chain fatty acids bacterial producers. The amelioration of the health status of the subjects was also established by the reduction of common infectious disease symptom incidence, the stimulation of the gut immune system showing a noteworthy variation of fecal β-defensin2 and calprotectin levels, and the modulation of the response of the respiratory tract’s immune system by salivary IgA as well as total antioxidant capacity biomarkers.
Article
Introduction: Intestinal microbiota affects human health and aging. The composition of intestinal microbiota and inflammation indices in elderly Chinese, especially centenarians, is unclear. Objective: This study aimed to explore the relationships between intestinal microbiota and inflammation in healthy housebound elders in Shanghai, China. Methods: We enrolled 156 differently aged adults and assigned them into 4 groups: those aged 35-64 years were assigned into Group AD; 65-79 years into Group YO; 80-94 years into Group MO; and 95-102 years into Group VO. Results: The diversity of intestinal microbiota in Group VO was significantly reduced compared with that of the other 3 groups. Bacteroidetes abundance in Group VO was significantly lower than that in Groups AD, YO, or MO; Proteobacteria abundance showed the opposite trend. Akkermansia, Bifidobacterium, and Lactobacillus abundance in Group VO was significantly higher than that in the other 3 groups; Anaerostipes, Butyricicoccus, and Faecalibacterium abundance showed the opposite trend. Solobacterium abundance in Group VO was significantly lower than that in the other 3 groups; Campylobacter, Porphyromonas, Escherichia, and Pseudomonas abundance showed the opposite trend. Plasma levels of tumor necrosis factor-α (TNF-α), IL-6, and IL-8 in Group VO were significantly higher than those in Groups AD, YO, and MO, while those in Group MO were significantly higher than those in Groups AD and YO. IL-1β and IL-10 plasma levels were not significantly different among the 4 groups. Proteobacteria abundance was positively correlated with TNF-α and IL-8 levels, while Campylobacter abundance was positively correlated with those of TNF-α and IL-6. Anaerostipes and Faecalibacterium abundance was negatively correlated with TNF-α and IL-6 levels. Conclusions: The diversity of intestinal microbiota in the oldest participants (centenarians) decreased significantly, with several beneficial bacterial strains showing increased or decreased abundance; harmful bacterial species showed a similar trend. Our oldest participants (centenarians) demonstrated significantly increased levels of pro-inflammatory cytokines, which may be related to inflammaging.
Article
Kawasaki disease (KD) and Henoch–Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment.
Article
Striving for longevity is neither a recent human desire nor a novel scientific field. The first article on this topic was published in 1838, when the average human life expectancy was approximately 40 years. Although nowadays people on average live almost as twice as long, we still (and perhaps more than ever) look for new ways to extend our lifespan. During this seemingly endless journey of discovering efficient methods to prolong life, humans were enthusiastic regarding several approaches, one of which is caloric restriction (CR). Where does CR, initially considered universally beneficial for extending both lifespan and health span, stand today? Does a lifelong decrease in food consumption represent one of the secrets of centenarians’ long and healthy life? Do we still believe that if we eat less, we will live longer? This review aims to summarize the current literature on CR as a potential life-prolonging intervention in humans and discusses metabolic pathways that underlie this effect.
Article
Background : Rhododendron nivale Hook. f (R.n), one of the four Manna Stash used in Tibetan medicine to delay aging, possesses anti-aging pharmacological activity. However, which R.n ingredients contain anti-aging properties and the underlying mechanisms involved are unclear. Hypothesis/Purpose Based on interactions between gut microbiota and natural medicines and the important role of gut microbiota in anti-aging, the study investigated the hypothesis that R.n possesses anti-aging properties and the interaction of gut microbiota with R.n is responsible for its anti-aging effects. Study Design : The primary active ingredients of R.n and their target function and pathway enrichment were explored. An aging mouse model was used to clarify the underlying anti-aging mechanisms of R.n. Methods : Chromatography, spectroscopy, nuclear magnetic technology, and pharmacology were used to reveal the major active ingredients of ethanol extract residues of R.n (RNEA). The target function and pathway enrichment of these active ingredients were explored. Plasma metabolomics coupled with intestinal flora evaluation and bioinformatics analysis was used to clarify the underlying anti-aging mechanisms of RNEA. Results : Myricetin-3-β-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-β-D-galactoside, and diplomorphanin B were separated and identified from RNEA. The network pharmacology study revealed that the active ingredients’ target function and pathway enrichment focused mainly on the glutathione antioxidant system. In a D-galactose-induced mouse model of aging, RNEA was shown to possess suitable anti-aging pharmacological activity, as indicated by the amelioration of memory loss and weakened superoxide dismutase and glutathione peroxidase activities. Plasma metabolomics coupled with intestinal flora examination and bioinformatics analysis revealed that RNEA could regulate the expression of glutathione-related enzymes and ameliorate D-galactose-induced imbalances in methionine, glycine, and serine, and betaine and galactose metabolism. The results showed that RNEA reshaped the disordered intestinal flora and mitigated the D-galactose-mediated decline in glutathione oxidase expression, further confirming that the anti-aging effect of RNEA was closely related to regulation of the glutathione antioxidant system. Conclusion : RNEA, consisting of myricetin-3-β-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-β-D-galactoside, and diplomorphanin B, possesses anti-aging activity. The anti-aging effect of RNEA might be due to reshaping intestinal flora homeostasis, increasing the expression of glutathione peroxidase 4 in the intestines and liver, enhancing glutathione peroxidase activity, and reinforcing the glutathione antioxidant system.
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Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a “younger-like phenotype” and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ. Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.
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This study provides the first comprehensive investigation of age patterning of gut microbiota of four human populations and three nonhuman primates and found that Prevotellamassilia , Prevotella , Gemmiger , Coprococcus , Faecalibacterium , and Roseburia may be common antiaging microbial markers in both humans and nonhuman primates due to their potential metabolic capabilities for host health benefits. Our results also provide key support for using macaques as animal models in studies of the gut microbiome’s role during human aging.
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Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation and response to cancer immunotherapies). Although primarily based on simple associations, there are nowadays an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. In this Review, we cover the history of the discovery of A. muciniphila and summarize the numerous findings and main mechanisms of action by which this intestinal symbiont improves health. A comparison of this microorganism with other next-generation beneficial microorganisms that are being developed is also made.
Article
Background Old age is characterized by a peculiar low-grade, chronic, and “sterile” inflammatory state, which has been termed “inflammaging.” This is believed to substantially contribute to the pathogenesis of many age-related diseases and to the progression of the ageing process. An adequate nutritional status is of great importance for maintaining proper immune system functionality and preventing frailty in the elderly. Methods The purpose of this narrative review is to synthesize what is known about the interaction between inflammaging and nutrition, focusing on the role of the Mediterranean diet, gut microbiota and calorie restriction (CR) in reducing systemic inflammation and improving clinical outcomes. Conclusions Dietary components may affect inflammation directly, counteracting the low grade age-related inflammation. In this regard, healthy diets, including the Mediterranean diet, are associated with lower concentrations of inflammatory mediators, like C-reactive protein (CRP) and Tumor Necrosis Factor-α (TNF-α), that are hallmarks of inflammaging. Among the components of a healthy diet, a higher intake of whole grains, vegetables and fruits, nuts and fish are all associated with lower inflammation. One area of promising research is the microbiome-ageing interaction. Indeed, dysbiosis plays a role in sub-optimal metabolism, immune function and brain function and contributes to the poor health and impaired well-being associated with ageing. Modulation of the gut microbiota has shown promising results in some disorders. Additionally, the discovery of several molecular pathways associated with ageing, and the characterization of the beneficial effects of calorie restriction (CR) in modulating metabolic pathways and preventing inflammation, should encourage research on CR mimetics, drugs able to promote lifespan and extend healthspan.
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High aerobic endurance capacity can be acquired by training and/or inherited. Aerobic exercise training (AET) and aging are linked to altered gut microbiome composition, but it is unknown if the environmental stress of exercise and host genetics that predispose for higher exercise capacity have similar effects on the gut microbiome during aging. We hypothesized that exercise training and host genetics would have conserved effects on the gut microbiome across different rodents. We studied young sedentary (Y-SED, 2-month-old) mice, old sedentary (O-SED, 26-month-old) mice, old mice with life-long AET (O-AET, 26-month-old), and aged rats selectively bred for high (HCR [High Capacity Runner], 21-month-old) and low (LCR [Low Capacity Runner], 21-month-old) aerobic capacity. Our results showed that O-SED mice had lower running capacity than Y-SED mice. The fecal microbiota of O-SED mice had a higher relative abundance of Lachnospiraceae, Ruminococcaceae, Turicibacteriaceae, and Allobaculum, but lower Bacteroidales, Alistipes, Akkermansia, and Anaeroplasma. O-AET mice had a higher running capacity than O-SED mice. O-AET mice had lower fecal levels of Lachnospiraceae, Turicibacteriaceae, and Allobaculum and higher Anaeroplasma than O-SED mice. Similar to O-AET mice, but despite no exercise training regime, aged HCR rats had lower Lachnospiraceae and Ruminococcaceae and expansion of certain Bacteroidales in the fecal microbiome compared to LCR rats. Our data show that environmental and genetic modifiers of high aerobic endurance capacity produce convergent gut microbiome signatures across different rodent species during aging. Therefore, we conclude that host genetics and life-long exercise influence the composition of the gut microbiome and can mitigate gut dysbiosis and functional decline during aging.
Article
The role of Akkermansia muciniphila, one of the most abundant microorganisms of the intestinal microbiota, has been studied extensively in metabolic diseases, such as obesity and diabetes. It is considered a next-generation probiotic microorganism. Although its mechanism of action has not been fully elucidated, accumulating evidence indicates the important role of A. muciniphila in brain functions via the gut-brain axis and its potential as a therapeutic target in various neuropsychiatric disorders. However, only a limited number of studies, particularly clinical studies, have directly assessed the therapeutic effects of A. muciniphila interventions in these disorders. This is the first review to discuss the comprehensive mechanism of A. muciniphila in the gut-brain axis via the protection of the intestinal mucosal barrier and modulation of the immune system and metabolites, such as short-chain fatty acids, amino acids, and amino acid derivatives. Additionally, the role of A. muciniphila and its therapeutic potential in various neuropsychiatric disorders, including Alzheimer's disease and cognitive deficit, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis, have been discussed. The review suggests the potential role of A. muciniphila in healthy brain functions.
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The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort studies across geographically distinct populations. We also address the promise of the targeted restoration of microorganisms associated with healthier ageing.
Chapter
This chapter brings in concepts from macroecology regarding diversity and trophic levels. Microbial diversity or richness could appear higher in some diseased conditions, especially when going beyond the gut microbiome. Single species dominance in the vaginal microbiome becomes more diverse in the majority of postmenopausal women, as the pH is no longer maintained as acidic. Nutrients and selective forces for in situ communities such as the skin and the oral microbiomes are briefly covered. Mucins, immunoglobulins, or even glycans expressed as blood group antigens, help microbes with localization and food. For the gut microbiome, the primary bioreactor is the ascending colon, while the microbes might spread out along the length of the colon, fermenting what they can ferment. Human genetics, historical contingency, and circadian rhythms all contribute to what we currently see in the microbiome, together with more studied factors such as nutrients and immune responses. Trophic levels in a human microbiome site may need to consider different scenarios of physiological states, during which different molecules are available, and different functions may be evolutionarily prioritized.
Chapter
The dramatic convergence of molecular biology, genomics, proteomics, metabolomics, bioinformatics, and artificial intelligence has provided a substrate for deep understanding of the biological basis of health and disease. Systems biology is a holistic, dynamic, integrative, cross-disciplinary approach to biological complexity that embraces experimentation, technology, computation, and clinical translation. Systems Medicine integrates genome analyses and longitudinal deep phenotyping with biological pathways and networks to understand mechanisms of disease, identify relevant blood biomarkers, define druggable molecular targets, and enhance the maintenance or restoration of wellness. Two programs initiated our understanding of data-driven population-based wellness. The Pioneer 100 Study of Scientific Wellness and the much larger Arivale commercial program that followed had two spectacular results: demonstrating the feasibility and utility of collecting longitudinal multiomic data, and then generating dense, dynamic data clouds for each individual to utilize actionable metrics for promoting health and preventing disease when combined with personalized coaching. Future developments in these domains will enable better population health and personal, preventive, predictive, participatory (P4) health care.
Chapter
Exposure to microorganisms and colonisation by them influence the development and function of essentially all organs, notably the immune, metabolic and central nervous systems. We therefore need to maintain essential microbial exposures, but this is often thought to conflict with the need to maintain hygiene to avoid disease-causing pathogens. This chapter suggests a framework for solving this conundrum. First, an evolutionary approach illuminates the two-way dialogue between host and microbiota and helps us to determine which exposures really are essential, and to question the role of the unnatural microbiota of the modern home. The evolutionary approach also helps us to understand the mechanisms of the health benefits derived from microbial inputs and the lifestyle changes that are distorting them. Importantly, distorted microbial exposures may explain much of the health deficit associated with low socioeconomic status (SES). By combining these insights with new understanding of the inherent Th2-adjuvanticity of some cleaning agents, and the non-specific immune system-modifying role of pathogens and of their replacement by the “trained immunity” effects of vaccines, it is possible to construct a framework for targeting hygiene and domestic cleaning in such a way that they protect us from pathogens while maintaining the essential microbial exposures.
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Aging is an inevitable process that all individuals experience, of which the extent differs among individuals. It has been recognized as the risk factor of neurodegenerative diseases by affecting gut microbiota compositions, microglia, and cognition abilities. Aging‐induced changes in gut microbiota compositions have a critical role in orchestrating the morphology and functions of microglia through the gut‐brain axis. Gut microbiota communicates with microglia by its secreted metabolites and neurotransmitters. This is highly associated with age‐related cognitive declines. Here, we review the main composition of microbiota in the aged individuals, outline the changes of the brain in age‐related cognitive decline from a neuroinflammation perspective, especially the changes of morphology and functions of microglia, discuss the crosstalk between microbiota and microglia in the aged brain and further highlight the role of microbiota‐microglia connections in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease). Microbiota‐microglia connection has been recognized in recent years. Aging‐induced changes of gut microbiota composition have a critical role in mediating the morphology and functions of microglia through gut‐brain axis, which is tightly related to age‐related cognitive decline. Here, we review the age‐related changes of gut microbiota and brain, and highlight the interaction between microbiota and microglia in the aged brain.
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Gut microbiota have recently been a topic of great interest in the field of microbiology, particularly their role in normal physiology and its influence on human health in disease. A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by gut microbiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive function in ageing. This review summarizes the evidence supporting the existence of such a connection and possible mechanisms of action whereby microbiota can influence the function of the central nervous system. Since normalisation of gut flora has been shown to prevent changes in behaviour, we further postulate on possible therapeutic targets to intervene with cognitive decline in ageing. The research poses various limitations, for example uncertainty about how this data translates to broad human populations. Nonetheless, the microbiota-gut-brain axis is an exciting field worthy of further investigation, particularly with regards to its implications on the ageing population.
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Introduction: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. Results: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10-25) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. Conclusions: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies.
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The etiology of periodontitis has traditionally been associated to a consortium of three bacterial species—the so-called “red-complex” of periodontal disease—which has been the target for most diagnostic and therapeutic strategies. However, other species have also been found to correlate with disease severity. In addition, the influence of smoking on periodontal microbiota is poorly understood. In the current manuscript, the composition of the subgingival microbiota in healthy individuals vs. patients with chronic periodontitis has been investigated using 16S pyrosequencing and the influence of smoking on periodontal composition has been examined. Subgingival bacterial communities were sampled from 82 patients: 22 non-smoking healthy controls, 28 non-smoking periodontal patients, and 32 smoking periodontal patients. Bacterial diversity was higher in periodontal patients than in healthy subjects, which could be interpreted as the consequence of a nutritionally richer environment or a reduced immune competence. Periodontal patients showed a significantly higher prevalence/relative abundance of “established” periopathogens but also other taxa whose role is not well-established and that should be targets for future research. These include Anaeroglobus, Bulleidia, Desulfobulbus, Filifactor, Mogibacterium, Phocaeicola, Schwartzia or TM7. The microbial community of smoking-associated periodontitis is less diverse and distinct from that of non-smokers, indicating that smoking has an influence on periodontal ecology. Interestingly, the high sequencing coverage allowed the detection at low proportions of periodontal pathogens in all healthy individuals, indicating that chronic periodontitis cannot be strictly considered an infectious disease but the outcome of a polymicrobial dysbiosis, where changes in the proportions of microbial consortia trigger the inflammatory and tissue-degradation responses of the host.
Conference Paper
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Objective: To compare the subgingival microbiome associated with health and chronic periodontitis by 16S pyrosequencing, analyzing the influence of smoking habit. Methods: Subgingival bacterial communities were sampled from 82 patients: 22 non-smoker healthy controls (NS-Controls), 28 non-smoker periodontal patients (NS-Perio) and 32 smoker periodontal patients (S-Perio). These samples were studied by pyrosequencing PCR products of the 16S ribosomal RNA gene. Results: In all the analyzed subgingival samples, 116 bacterial genera were identified. The most abundant genus in all patients was Fusobacterium (48%-32%). In comparison to the NS-Controls, the NS-Perio and the S-Perio showed a significantly higher prevalence of patients with presence for Anaeglobus, Bulleidia, Desulfobulbus, Eubacterium, Filifactor, Mogibacterium, Mycoplasma, Phocaeicola, Schwartzia, Tannerella and Treponema (Fisher’s exact test, p<0.05). With respect to the influence of smoking habit, Anaeroglobus, Bulleidia, Corynebacterium and Granulicatella were more prevalent in the S-Perio than in the NS-Perio (Fisher’s exact test, p<0.05). In comparison to the NS-Controls, the periodontal patient groups had significantly higher percentages of abundance of Filifactor, Porphyromonas, Tannerella, Treponema, Atopobium, Eubacterium, Peptostreptococcus and TM7 (Kruskal-Wallis test, p<0.05). With respect to the influence of smoking habit, TM7 and Veillonella were more abundant in the S-Perio than in the NS-Perio (3% and 2% versus 1% and 0.5% respectively), while Porphyromonas presented a significantly lower value in the S-Perio (16% versus 26%) (U Mann-Whitney test, p<0.05). Rarefaction curves and diversity indices showed a greater number of bacterial species in samples from periodontal patients (mainly non-smokers), appearing species undetected in the NS-Controls. Conclusion: 16S pyrosequencing allowed to demonstrate the different composition and greater diversity of subgingival microbiome in chronic periodontitis, confirming the association of putative periodontal pathogens and implicating a number of other taxa that will be targets for future research. The microbial profile of smoking-associated periodontitis is less diverse and distinct from that of non-smokers.
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Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
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The human gut represents a highly complex ecosystem, which is densely colonized by a myriad of microorganisms that influence the physiology, immune function and health status of the host. Among the many members of the human gut microbiota, there are microorganisms that have co-evolved with their host and that are believed to exert health-promoting or probiotic effects. Probiotic bacteria isolated from the gut and other environments are commercially exploited, and although there is a growing list of health benefits provided by the consumption of such probiotics, their precise mechanisms of action have essentially remained elusive. Genomics approaches have provided exciting new opportunities for the identification of probiotic effector molecules that elicit specific responses to influence the physiology and immune function of their human host. In this review, we describe the current understanding of the intriguing relationships that exist between the human gut and key members of the gut microbiota such as bifidobacteria and lactobacilli, discussed here as prototypical groups of probiotic microorganisms.
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16S ribosomal RNA gene (rDNA) amplicon analysis remains the standard approach for the cultivation-independent investigation of microbial diversity. The accuracy of these analyses depends strongly on the choice of primers. The overall coverage and phylum spectrum of 175 primers and 512 primer pairs were evaluated in silico with respect to the SILVA 16S/18S rDNA non-redundant reference dataset (SSURef 108 NR). Based on this evaluation a selection of ‘best available’ primer pairs for Bacteria and Archaea for three amplicon size classes (100–400, 400–1000, ≥1000 bp) is provided. The most promising bacterial primer pair (S-D-Bact-0341-b-S-17/S-D-Bact-0785-a-A-21), with an amplicon size of 464 bp, was experimentally evaluated by comparing the taxonomic distribution of the 16S rDNA amplicons with 16S rDNA fragments from directly sequenced metagenomes. The results of this study may be used as a guideline for selecting primer pairs with the best overall coverage and phylum spectrum for specific applications, therefore reducing the bias in PCR-based microbial diversity studies.
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Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.
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Illumina paired-end reads are used to analyse microbial communities by targeting amplicons of the 16S rRNA gene. Publicly available tools are needed to assemble overlapping paired-end reads while correcting mismatches and uncalled bases; many errors could be corrected to obtain higher sequence yields using quality information. PANDAseq assembles paired-end reads rapidly and with the correction of most errors. Uncertain error corrections come from reads with many low-quality bases identified by upstream processing. Benchmarks were done using real error masks on simulated data, a pure source template, and a pooled template of genomic DNA from known organisms. PANDAseq assembled reads more rapidly and with reduced error incorporation compared to alternative methods. PANDAseq rapidly assembles sequences and scales to billions of paired-end reads. Assembly of control libraries showed a 4-50% increase in the number of assembled sequences over naïve assembly with negligible loss of "good" sequence.
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Cytoscape is a popular bioinformatics package for biological network visualization and data integration. Version 2.8 introduces two powerful new features—Custom Node Graphics and Attribute Equations—which can be used jointly to greatly enhance Cytoscape's data integration and visualization capabilities. Custom Node Graphics allow an image to be projected onto a node, including images generated dynamically or at remote locations. Attribute Equations provide Cytoscape with spreadsheet-like functionality in which the value of an attribute is computed dynamically as a function of other attributes and network properties. Availability and implementation: Cytoscape is a desktop Java application released under the Library Gnu Public License (LGPL). Binary install bundles and source code for Cytoscape 2.8 are available for download from http://cytoscape.org. Contact: msmoot@ucsd.edu
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Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
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Several different protocols are used for fecal DNA extraction, which is an integral step in all phylogenetic and metagenomic approaches to characterize the highly diverse intestinal ecosystem. We compared four widely used methods, and found their DNA yields to vary up to 35-fold. Bacterial, archaeal and human DNA was quantified by real-time PCR, and a compositional analysis of different extracts was carried out using the Human Intestinal Tract Chip, a 16S rRNA gene-based phylogenetic microarray. The overall microbiota composition was highly similar between the methods in contrast to the profound differences between the subjects (Pearson correlations >0.899 and 0.735, respectively). A detailed comparative analysis of mechanical and enzymatic methods showed that despite their overall similarity, the mechanical cell disruption by repeated bead beating showed the highest bacterial diversity and resulted in significantly improved DNA extraction efficiency of archaea and some bacteria, including Clostridium cluster IV. By applying the mechanical disruption method a high prevalence (67%) of methanogenic archaea was detected in healthy subjects (n=24), exceeding the typical values reported previously. The assessment of performance differences between different methodologies serves as a concrete step towards the comparison and reliable meta-analysis of the results obtained in different laboratories.
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The aging phenotype in humans is very heterogeneous and can be described as a complex mosaic resulting from the interaction of a variety of environmental, stochastic and genetic-epigenetic variables. Therefore, each old person must be considered as a singleton, and consequently the definition of 'aging phenotype' is very difficult. We discuss the phenotype of centenarians, the best example of successful aging, as well as other models exploited to study human aging and longevity, such as families enriched in long-living subjects, twins and cohorts of unrelated subjects. A critical review of literature available until March 2008. No single model can be considered the gold standard for the study of aging and longevity, instead the combination of results obtained from different models must be considered in order to better understand these complex phenomena. We propose that a systems biology concept such as that of 'bow-tie' architecture, useful for managing information flow, could help in this demanding task.
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Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.
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Although survival to old age is known to have strong environmental and behavioral components, mortality differences between social groups tend to diminish or even disappear at older ages. Hypothesizing that surviving to extreme old age entails a substantial familial predisposition for longevity, we analyzed the pedigrees of 444 centenarian families in the United States. These pedigrees included 2,092 siblings of centenarians, whose survival was compared with 1900 birth cohort survival data from the U.S. Social Security Administration. Siblings of centenarians experienced a mortality advantage throughout their lives relative to the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half the national level; male siblings had a similar advantage at most ages, although diminished somewhat during adolescence and young adulthood. Relative survival probabilities for these siblings increase markedly at older ages, reflecting the cumulative effect of their mortality advantage throughout life. Compared with the U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely to attain age 100 themselves, while female siblings were at least 8 times as likely.
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The gut microbiota (GM) is an important regulator of body homeostasis, including intestinal and extra-intestinal effects. This review focuses on the gut microbiota-bone axis, which we define as the impartial effect of the gut-associated microbial community or the molecules they synthesize, on bone health. While research in this field is limited, findings from preclinical studies support that gut microbes positively impact bone mineral density and strength parameters. Moreover, administration of beneficial bacteria (probiotics) in preclinical models has demonstrated higher bone mineralization and greater bone strength. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus and thus lactobacilli are among the best candidates for future clinical intervention trials. However, their effectiveness is dependent on stage of development, as early life constitutes an important time for impacting bone health, perhaps via modulation of the GM. In addition, sex-specific difference also impacts the efficacy of the probiotics. Although auspicious, many questions regarding the gut microbiota-bone axis require consideration of potential mechanisms; sex-specific efficacy; effective dose of probiotics; and timing and duration of treatment.
In the past few years, increasing evidence has suggested that alterations of the epithelial barrier of the GI tract are linked to both local and systemic disorders of various natures. However, in spite of the numerous debilitating health problems that might stem from it, very little attention has been given to how ageing affects this critical structure. Here, the most recent data on the age-associated modifications of some of the physical and immunological features of intestinal epithelial barrier are discussed along with potential strategies to restore its function and improve the quality of life of the elderly, an ever increasing demographic segment of our society.
Article
The purpose of this study was to evaluate the microbial community (MC) composition as it relates to salivary metabolites and periodontal clinical parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled equally into 5 categories of periodontal status per the biofilm-gingival interface classification. Microbial species within subgingival plaque samples were identified by human microbiome identification microarray. Whole saliva was analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry for metabolite identification. Phylum was grouped into MCs according to principal component analysis. Generalized linear and regression models were used to examine the association among MC, species, periodontal clinical parameters, and salivary metabolome. Multiple comparisons were adjusted with the false discovery rate. The study population was distributed into 8 distinct MC profiles, designated MC-1 to MC-8. MC-2 explained 14% of the variance and was dominated by Synergistetes and Spirochaetes. It was the only community structure significantly associated with high probing depth (P = 0.02) and high bleeding on probing (P = 0.008). MC-2 was correlated with traditional periodontal pathogens and several newly identified putative periodontal pathogens: Fretibacterium fastidiosum, Fretibacterium sp. OT360/OT362, Filifactor alocis, Treponema lecithinolyticum, Eubacterium saphenum, Desulfobulbus sp./OT041, and Mogibacterium timidum. Synergistetes phylum was strongly associated with 2 novel metabolites-cyclo (-leu-pro) and cyclo (-phe-pro)-at 21 d of biofilm overgrowth (P = 0.02). In subjects with severe periodontitis (P2 and P3), cyclo (-leu-pro) and cyclo (-phe-pro) were significantly associated with increased changes in probing depth at 21 d of biofilm overgrowth (P ≤ 0.05). The analysis identified a MC dominated by Synergistetes, with classic and putative newly identified pathogens/pathobionts associated with clinical disease. The metabolomic discovery of 2 novel cyclodipeptides that have been reported to serve as quorum-sensing and/or bacteriocidal/bacteriostatic molecules, in association with Synergistetes, suggests a potential role in periodontal biofilm dysbiosis and periodontal disease that warrants further investigation. © International & American Associations for Dental Research 2015.
Article
Increasing evidences suggest that gut microbiota underpin the development of health and longevity. However, our understanding of what influences the composition of this community of the longevous has not been adequately described. Therefore, illumina sequencing analysis was performed on the gut microbiota of centenarians (aged 100-108 years; RC) and younger elderlies (aged 85-99 years; RE) living in Bama County, Guangxi, China and the elderlies (aged 80-92 years; CE) living in Nanning city, Guangxi, China. In addition, their dietary was monitored using a semi-quantitative dietary questionary (FFQ 23). The results revealed the abundances of Roseburia and Escherichia were significantly greater, whereas Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella and Akkermansia were significantly less in centenarians at the genus level. Both clustering analysis and UniFraq distance analysis showed structural segregation with age and diet among the three populations. Using partial least square discriminate analysis and redundancy analysis, we identified thirty-three and thirty-four operational taxonomic units (OTUs) as key OTUs that were significantly associated with age and diet, respectively. Age-related OTUs were characterized as Ruminococcaceae, Clostridiaceae and Lachnospiraceae and the former two were increased in the centenarians; Diet-related OTUs were classified as Bacteroidales, Lachnospiraceae and Ruminococcaceae. The former two were deceased, whereas the later one was increased in the high-fiber diet. The age and high-fiber diet are concomitant with changes in the gut microbiota of centenarians, suggesting that age and high-fiber diet can establish a new structurally balanced architecture of gut microbiota that may benefit health benefit of the centenarians.
Article
Subgingival microorganisms are potentially associated with periodontal diseases. However, changes in the subgingival microbiota during the progress of periodontal diseases are poorly understood. In this study, we analyzed bacterial communities in the subgingival paper point samples from 32 Korean individuals with no sign of disease, gingivitis, or periodontitis using 454 FLX Titanium pyrosequencing. A total of 256,113 reads representing 26 phyla, 433 genera, and 1,016 species were detected. Bacteroidetes, Fusobacteria, Synergistetes, and Spirochaetes were the abundant phyla in periodontitis subjects, whereas Firmicutes and Proteobacteria were identified as the dominant phyla in the gingivitis and healthy subjects, respectively. Although high levels of Porphyromonas, Fusobacterium, Fretibacterium, Rothia, Filifactor, and Treponema genera were observed in the periodontitis subjects, Streptococcus, Capnocytophaga, Leptotrichia, and Haemophilus genera were found at high frequency in the gingivitis subjects. Species including Porphyromonas gingivalis, Fusobacterium nucleatum, and Fretibacterium fastidiosum were significantly increased in periodontitis subjects. On the other hand, Streptococcus pseudopneumoniae, Haemophilus parainfluenzae, and Leptotrichia hongkongensis were preferentially observed in the gingivitis subjects. Intriguingly, the halophile Halomonas hamiltonii was revealed as a predominant species in the healthy subjects. Based on Fast UniFrac analysis, distinctive bacterial clusters were classified for the healthy, gingivitis, and periodontitis state. The current findings might be useful for understanding the pathogenesis, diagnosis, and treatment of periodontal diseases. © International & American Associations for Dental Research 2015.
Article
Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, including 416 twin pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a co-occurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germ-free mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism.
Article
Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal microbiota-host mutualistic interaction, compromising the possibility to reach longevity. In this scenario, the NU-AGE project involves the development of dietary interventions specifically tailored to the maintenance of a healthy trajectory of the intestinal microbiome, counteracting all processes connected to the pathophysiology of the human aging.
Article
Hypothesis-testing methods for multivariate data are needed to make rigorous probability statements about the effects of factors and their interactions in experiments. Analysis of variance is particularly powerful for the analysis of univariate data. The traditional multivariate analogues, however, are too stringent in their assumptions for most ecological multivariate data sets. Non-parametric methods, based on permutation tests, are preferable. This paper describes a new non-parametric method for multivariate analysis of variance, after McArdle and Anderson (in press). It is given here, with several applications in ecology, to provide an alternative and perhaps more intuitive formulation for ANOVA (based on sums of squared distances) to complement the description provided by McArdle and Anderson (in press) for the analysis of any linear model. It is an improvement on previous non-parametric methods because it allows a direct additive partitioning of variation for complex models. It does this while maintaining the flexibility and lack of formal assumptions of other non-parametric methods. The test-statistic is a multivariate analogue to Fisher’s F-ratio and is calculated directly from any symmetric distance or dissimilarity matrix. P-values are then obtained using permutations. Some examples of the method are given for tests involving several factors, including factorial and hierarchical (nested) designs and tests of interactions.
Article
Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch.
Article
The Index of Independence in Activities of Daily Living (ADL), now in frequent use in rehabilitation settings, has application for prevention of disability and maintenance of rehabilitation gains in the aging person in all settings. Since the Index is sensitive to changes in meaningful self-care functions, uses well-defined criteria, and can be broadly taught to non-professionals, it has considerable practical value as a longitudinal measure of change and predictor of adaptive capacity in terms of community residences and congregate living facilities.
Please cite this article in press as
  • Biagi
Please cite this article in press as: Biagi et al., Gut Microbiota and Extreme Longevity, Current Biology (2016), http://dx.doi.org/10.1016/ j.cub.2016.04.016
1195-1204. exception of the network involving all samples (A) for which the genera present in at least one of the other networks were plotted. Co-occurrence groups
  • F Wang
  • T Yu
  • G Huang
  • D Cai
  • X Liang
  • H Su
  • Z Zhu
  • D Li
  • Y Yang
  • P Shen
Wang, F., Yu, T., Huang, G., Cai, D., Liang, X., Su, H., Zhu, Z., Li, D., Yang, Y., Shen, P., et al. (2015). Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. J. Microbiol. Biotechnol. 25, 1195-1204. exception of the network involving all samples (A) for which the genera present in at least one of the other networks were plotted. Co-occurrence groups (COGs) are named after the included genera with the highest relative abundance and are color coded as follows: Bacteroides COG (yellow);