Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model.

Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.

Human microbiome variance is underestimated.

Most of the variance in the human microbiome remains unexplained. Although an extensive list of individual lifestyles shaping the microbiome has been identified, important gaps in knowledge persist. Most human microbiome data are from individuals living in socioeconomically developed countries. This may have skewed the interpretation of microbiome variance and its relationship to health and disease. Moreover, striking under-representation of minority groups in microbiome studies is a missed opportunity to assess context, history and the changing nature of the microbiome in relation to the risk of disease. Therefore, we focus here on areas of recent progress - ageing and ethnicity - both of which contribute to microbiome variance with particular lessons for the promise of microbiome-based diagnostics and therapeutics.

The nonindustrialised microbiome in a modern world.

The microbiome contributes to human development and maturation, and is essential for maintenance of health and prevention of disease. While the human genome encodes one's identity, the microbiome - also individually unique - provides a window on one's lifestyle and exposure to environmental variables. The microbiome thus serves as a biomarker of host health and a driver of certain diseases. However, current understanding of the gut microbiome is largely based on studies of industrialised peoples of North America and Europe. Gaps in knowledge of the microbiomes of other groups, particularly those in developing or nonindustrialised societies, are important, particularly in view of contrasting epidemiological risks of acquiring chronic inflammatory and metabolic disorders. Here, we explore underlying mechanisms of microbiome differences and whether the potential benefits of nonindustrialised microbiome can be realised in a modern world.

The Healthy Microbiome-What Is the Definition of a Healthy Gut Microbiome?

Use of microbiome-based biomarkers in diagnosis, prognosis, risk profiling, and precision therapy requires definition of a healthy microbiome in different populations. To determine features of the intestinal microbiota associated with health, however, we need improved microbiome profiling technologies, with strain-level resolution. We must also learn more about how the microbiome varies among apparently healthy people, how it changes with age, and the effects of diet, medications, ethnicity, geography, and lifestyle. Furthermore, many intestinal microbes, including viruses, phage, fungi, and archaea, have not been characterized, and little is known about their contributions to health and disease.Whether a healthy microbiome can be defined is an important and seemingly simple question, but with a complex answer in continual need of refinement.

Whole Blueberry and Isolated Polyphenol-Rich Fractions Modulate Specific Gut Microbes in an In Vitro Colon Model and in a Pilot Study in Human Consumers.

Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB-namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)-to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits.

Arrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes.

Lifestyle, obesity, and the gut microbiome are important risk factors for metabolic disorders. We demonstrate in 1,976 subjects of a German population cohort (KORA) that specific microbiota members show 24-h oscillations in their relative abundance and identified 13 taxa with disrupted rhythmicity in type 2 diabetes (T2D). Cross-validated prediction models based on this signature similarly classified T2D. In an independent cohort (FoCus), disruption of microbial oscillation and the model for T2D classification was confirmed in 1,363 subjects. This arrhythmic risk signature was able to predict T2D in 699 KORA subjects 5 years after initial sampling, being most effective in combination with BMI. Shotgun metagenomic analysis functionally linked 26 metabolic pathways to the diurnal oscillation of gut bacteria. Thus, a cohort-specific risk pattern of arrhythmic taxa enables classification and prediction of T2D, suggesting a functional link between circadian rhythms and the microbiome in metabolic diseases.

Adjusting for age improves identification of gut microbiome alterations in multiple diseases.

Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-microbiome associations display specific age-centric trends. Ageing-associated microbiome alterations towards a disease-like configuration occur in colorectal cancer patients, thereby masking disease signatures. We identified a microbiome disease response shared across multiple diseases in elderly subjects that is distinct from that in young/middle-aged individuals, but also a novel set of taxa consistently gained in disease across all age groups. A subset of these taxa was associated with increased frailty in subjects from the ELDERMET cohort. The relevant taxa differentially encode specific functions that are known to have disease associations.

The human body is an ecosystem made up of both human cells and trillions of microbes, and the largest microbial community is in the gut. This community of gut microbes helps harvest nutrients from our food, modulates our immune system, and even affects our mood. Infectious and chronic diseases appear to cause changes in the make-up of the gut microbiome, while microbiome changes may increase the risk of some non-infectious diseases. Learning more about these disease-linked changes in the gut microbiome may therefore help scientists to develop new tests and treatments. To do this, scientists need to understand which microbes play a role in individual diseases, if risk-related microbes are gained or helpful microbes lost in patients with particular diseases, and if certain changes in gut microbes occur across many diseases. Ageing also changes the gut microbes. This may happen because older individuals eat a less complex diet and are likely to take many medications that may alter the microbes in their gut. Because of this, age may affect changes in gut microbes associated with diseases. This highlights the need for studies that tease apart the importance of ageing-related and disease-related changes in the gut microbiome. Now, Ghosh et al. show that gut microbe changes linked to diseases may vary with a person's age. The analysis compared the gut microbiomes of more than 2,500 individuals aged 20 to 89. This included individuals with inflammatory bowel disease, colorectal cancer, type 2 diabetes, intestinal polyps and liver cirrhosis. The study revealed that younger people gradually gain disease-associated gut microbes, while older people tend to lose the gut microbes usually found in a healthy gut. Ghosh et al. also identified a set of gut microbes that were gained in many diseases and across age-groups. This set of microbes was also associated with frailty in elderly people. The characteristics of the microbes in this set are all known to have detrimental effects on human health. This analysis shows how important it is to control for age and other factors that may skew the results of microbiome projects. Future studies are needed to understand why these gut microbe changes occur and what the consequences of these changes are for a person's health and the course of their disease. This may lead to the development of treatment strategies that help promote a healthy gut microbiome and fight disease throughout life.

Composition and Functional Characterization of Microbiome Associated with Mucus of the Coral Fungia echinata Collected from Andaman Sea.

This study describes the community composition and functions of the microbiome associated with the mucus of the coral Fungia echinata based on metagenomic approach. Metagenome sequence data showed a dominance of the class Gammaproteobacteria followed by Alphaproteobacteria, Betaproteobacteria, Deltaproteobacteria, Flavobacteriia, Bacilli, and Clostridia. At the order level, the most abundant groups were Pseudomonadales, Oceanospirillales, Alteromonadales, and Rhodobacterales. The genus Psychrobacter was the most predominant followed by Thalassolituus and Cobetia, although other genera were also present, such as Sulfitobacter, Pseudoalteromonas, Oleispira, Halomonas, Oceanobacter, Acinetobacter, Pseudomonas, Vibrio, and Marinobacter. The metabolic profile of the bacterial community displayed high prevalence of genes associated with core-housekeeping processes, such as carbohydrates, amino acids, proteins, and nucleic acid metabolism. Further, high abundance of genes coding for DNA replication and repair, stress response, and virulence factors in the metagenome suggested acquisition of specific environmental adaptation by the microbiota. Comparative analysis with other coral metagenome exhibits marked differences at the taxonomical and functional level. This study suggests the bacterial community compositions are influenced by the specific coral micro-niche and the oligotrophic marine environment.

Taxonomic and functional characteristics of microbial communities and their correlation with physicochemical properties of four geothermal springs in Odisha, India.

This study describes microbial diversity in four tropical hot springs representing moderately thermophilic environments (temperature range: 40-58°C; pH: 7.2-7.4) with discrete geochemistry. Metagenome sequence data showed a dominance of Bacteria over Archaea; the most abundant phyla were Chloroflexi and Proteobacteria, although other phyla were also present, such as Acetothermia, Nitrospirae, Acidobacteria, Firmicutes, Deinococcus-Thermus, Bacteroidetes, Thermotogae, Euryarchaeota, Verrucomicrobia, Ignavibacteriae, Cyanobacteria, Actinobacteria, Planctomycetes, Spirochaetes, Armatimonadetes, Crenarchaeota, and Aquificae. The distribution of major genera and their statistical correlation analyses with the physicochemical parameters predicted that the temperature, aqueous concentrations of ions (such as sodium, chloride, sulfate, and bicarbonate), total hardness, dissolved solids and conductivity were the main environmental variables influencing microbial community composition and diversity. Despite the observed high taxonomic diversity, there were only little variations in the overall functional profiles of the microbial communities in the four springs. Genes involved in the metabolism of carbohydrates and carbon fixation were the most abundant functional class of genes present in these hot springs. The distribution of genes involved in carbon fixation predicted the presence of all the six known autotrophic pathways in the metagenomes. A high prevalence of genes involved in membrane transport, signal transduction, stress response, bacterial chemotaxis, and flagellar assembly were observed along with genes involved in the pathways of xenobiotic degradation and metabolism. The analysis of the metagenomic sequences affiliated to the candidate phylum Acetothermia from spring TB-3 provided new insight into the metabolism and physiology of yet-unknown members of this lineage of bacteria.