LONGECITY

"...Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis..."

"...In this study, we present the GMHI, a simple and biologically interpretable metric to quantify the likelihood of disease presence from a gut microbiome sample..."

"...When demonstrating the potential of GMHI on independent validation datasets, we obtained strong prediction results for healthy individuals, and for cohorts with autoimmunity and liver disease. The strong reproducibility on validation datasets suggests that sufficient dataset integration across a large population could lead to robust predictors of health. This may be due, in part, to the signature encompassing more of the heterogeneity across various sources and conditions, while amplifying signal (against noise) from the repeated phenotype characteristics..."

Gupta, V.K., Kim, M., Bakshi, U. et al. A predictive index for health status using species-level gut microbiome profiling. Nat Commun 11, 4635 (2020). https://doi.org/10.1...467-020-18476-8

Two potentially powerful instruments:

Optimum health and inhibition of cancer progression by microbiome and resveratrol

"Resveratrol (RES) is a naturally occurring polyphenol found in fruits, green leafy vegetables, and peanuts. This versatile compound, which has potent regenerative, anti-oxidative, and cancer-fighting properties, is produced in plants, particularly in response to stress stimuli. By various mechanisms, including regulation of genes and proteins, RES inhibits the growth of pathogenic bacteria and the development of cancers. The gut has a prominent role in nutrient assimilation, metabolism, immunity, and cancer regression, and the endogenous microbiome protects the host from invasive bacteria that facilitate the progression of various diseases. Short-chain fatty acids (SFCAs) are the byproducts of microbial fermentation in the gastrointestinal tract. Native microflora regulates internal homeostasis, influence the activity of host immune cells, and regress some cancers via the action of SCFAs produced from a plant-based diet. This review shows the relevance of dietary constituents and gut microbial activity in ensuring optimal health of the host."

https://pubmed.ncbi....h.gov/33049680/

"Understanding how dietary nutrients modulate the gut microbiome is of great interest for the development of food products and eating patterns for combatting the global burden of non-communicable diseases. In this narrative review we assess scientific studies published from 2005 to 2019 that evaluated the effect of micro- and macro-nutrients on the composition of the gut microbiome using in vitro and in vivo models, and human clinical trials. The clinical evidence for micronutrients is less clear and generally lacking. However, preclinical evidence suggests that red wine- and tea-derived polyphenols and vitamin D can modulate potentially beneficial bacteria. Current research shows consistent clinical evidence that dietary fibers, including arabinoxylans, galacto-oligosaccharides, inulin, and oligofructose, promote a range of beneficial bacteria and suppress potentially detrimental species. The preclinical evidence suggests that both the quantity and type of fat modulate both beneficial and potentially detrimental microbes, as well as the Firmicutes/Bacteroides ratio in the gut. Clinical and preclinical studies suggest that the type and amount of proteins in the diet has substantial and differential effects on the gut microbiota. Further clinical investigation of the effect of micronutrients and macronutrients on the microbiome and metabolome is warranted, along with understanding how this influences host health." (bold mine)

Yang, Q.; Liang, Q.; Balakrishnan, B.; Belobrajdic, D.P.; Feng, Q.-J.; Zhang, W. Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review. Nutrients 2020, 12, 381.https://www.mdpi.com...2-6643/12/2/381

Soluble fiber has (likely) the biggest impact on the microbiome-longevity link, as it is fermented by gut bacteria into SCFAs. Exercise training can also increase fecal SCFAs, which impact lifespan in mice:

Gut Microbiome Implicated in Healthy Aging and Longevity

https://isbscience.o...-and-longevity/

https://www.nature.c...255-021-00348-0

"...The major findings of our analysis were: 1) individual gut microbiomes became increasingly more unique with age, starting in mid-to-late adulthood, and this uniqueness was positively associated with known microbial metabolic markers for health and longevity; 2) the increase in microbiome uniqueness with age occurred in both males and females, but was 50% more pronounced in females; 3) in the later decades of human lifespan, healthy individuals continued to show an increasingly unique gut microbial compositional state with age, while that pattern was absent in those in worse health; 4) in individuals approaching extreme age (85+ years old), retaining high relative Bacteroides abundance and having a low gut microbiome uniqueness score were both associated with decreased survival in the course of 4 year follow-up. These observations are strengthened by the presence of similar age-related trends in two separate cohorts, and the replication of associations with health and longevity in a validation cohort. Our findings indicate that healthy aging of the gut microbiome involves depletion of core microbes and their replacement by less common taxa, resulting in increasingly distinc microbiomes. These findings are consistent with patterns previously reported in centenarians across the world (6, 7), despite the fact that dominant genera (the core microbiome) often vary across cultures and geographic locations (24). This variability posts a major challenge to identifying universal gut microbial signatures of health and disease..."

https://www.biorxiv.....02.26.966747v1

In case you missed it, pretty actual these days and emphasizing the importance of soluble fibers:

https://www.longecit...me/#entry903627

Increasing evidence:

https://longevity.te...-and-longevity/

"The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood."

https://www.nature.c...255-021-00348-0

Gut Bacteria Boost Host NAD Metabolism

https://www.youtube....h?v=cPE1fJJSVcE

 

Gut Bacteria Boost Host NAD Metabolism

 

https://www.youtube....h?v=cPE1fJJSVcE

 

The audio on the link above isn't good, this links is better:

"Results We identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (false discovery rate<0.05). Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways. The opposite was found for plant foods and fish, which were positively associated with short-chain fatty acid-producing commensals and pathways of nutrient metabolism."

Bolte LA, Vich Vila A, Imhann F, et al Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome Gut Published Online First: 02 April 2021. doi: 10.1136/gutjnl-2020-322670

I saw that paper last week, but good find albedo!

Nice infographic summary of interaction between host and microbiota. Note how inflammation is one of the major mechanisms for 9/10 host listed environments:

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https://pubmed.ncbi....h.gov/33989551/

I always thought that a 'bad'/onesided microbiome is bad for healthspan as well as lifespan, and  that conversely good is good!

As always it's more complicated. In this study Drosophila that had been raised without a microbiome showed less of the hallmarks of aging at advanced age than standard flies and lived considerably longer! 

The authors hypothesize that a standard microbiome may cause some of the hallmarks of aging. Their discussion ranges  more wide so it seemed useful to upload the full report.

 Micrbiome.pdf   3.73MB   4 downloads

Great finding Harkijn!

I wonder what this would imply for those of us on finasteride or dutasteride (inhibitors of the 5α-reductase) for our microbiota:

"Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases^1,2,3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis."

https://www.nature.c...586-021-03832-5

I wonder what this would imply for those of us on finasteride or dutasteride (inhibitors of the 5α-reductase) for our microbiota:

 

"Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases^1,2,3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis."

 

https://www.nature.c...586-021-03832-5

Secondary bile acids are derived from cholesterol. Although relatively higher cholesterol is associated with an increased CVD risk, conversely, for those who escape that, higher cholesterol is associated with a lower all-cause mortality risk in older adults. I'd bet that centenarians metabolize cholesterol into these secondary bile acids, which may be contributing to their longevity. 

Du Y, Gao Y, Zeng B, Fan X, Yang D, Yang M. Effects of anti-aging interventions on intestinal microbiota. Gut Microbes. 2021;13(1):1994835.

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Interesting: the "European Food Safety Authority (EFSA) delivered an opinion that heat-treated Akkermansia muciniphila is safe for use as a novel food in the European Union". So this is inanimate pasteurized A. muciniphila. I wonder if and what health claim can be made but it is good progress.

https://isappscience...val-and-beyond/

From the MIT Press:

The Invisible Organ Shaping Our Lives: Milestones in Human Microbiota Research

Despite the cautionary statement of this review (in proof) it is interesting to check the impact of some of the interventions available to us (eg CR, IF, Keto, pro/prebiotics, ...bold=clinical, bold-red=preclinical and clinical models):

"Scope of Review
This review provides an overview of the role of the gut microbiota in the physiological and metabolic alterations observed in two body weight dysregulation-related disorders, obesity and cachexia. Secondly, we synthesis the available evidence for different strategies’ – including caloric restriction, intermittent fasting, ketogenic diet, bariatric surgery, probiotics, prebiotics, synbiotics, high-fibre diet and fermented foods – effects on body weight and gut microbiota composition. This approach was used to give insights on the possible link between body weight control and gut microbiota configuration.

Major Conclusions
Despite extensive associations between body weight and gut microbiota composition, there has been limited success in the translation of microbiota-related interventions for body weight control in humans. Manipulation of the gut microbiota alone is insufficient to alter body weight and future research is needed combining strategies to enhance the effects of lifestyle interventions."

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Has anyone used this akkermansia supplement: https://pendulumlife...lum-akkermansia

Informative thread! So let's say you find out after your tests that you are in need of some specific strains.  Where and how to get those?  Going to amazon or just buying a commercial probiotic you get lot of unnecessary strains and some that may be even harmful to you depending on various conditions like your genetic mutations, etc.  So is there a reliable service that can make custom probiotic blends for you based on your microbiome testing report?

This looks to be a decent resource for probiotics:  https://www.probioticadvisor.com/

Zhou X, Baumann R, Gao X, et al. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. Cell. 2022;185(19):3467-3486.e16.

https://www.cell.com...8674(22)01115-1

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Vijay, A., Valdes, A.M. Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutr 76, 489–501 (2022). https://doi.org/10.1...430-021-00991-6

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"The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique
characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating
information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture
to reveal the unique gut microbial structure of the world’s longevity town—Jiaoling, China, centenarians and people of different
ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was
explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians.
Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation
and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic
Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl
Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated
2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear
complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent
intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore
the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as
antioxidant systems may contribute to health and longevity."

Wu, L., Xie, X., Li, Y. et al. Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus. npj Biofilms Microbiomes 8, 102 (2022). https://doi.org/10.1...522-022-00366-0

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Does anyone out there have some experience with Myota company in UK?

https://myotahealth.com/

"... animal studies have confirmed that aging can be delayed by FMT, probiotics, diet, and other regulation of the gut microbiota. However, the specific microbial characteristics related to delayed aging and maintenance of youth still need to be combined with several related experimental results for professional summary analysis. One researcher found a higher abundance of favorable bacteria in all of the experimental mice coexisting in the young trait-associated gut microbiota by Euler–Venn analysis (Li et al., 2021). Human-delayed aging trials should be considered in many aspects, focusing on overall variations in the intestinal microbiota. Lifelong monitoring of the microbiota can be considered. A relevant platform needs to be developed to achieve big data integration and efficient use of experimental data, reliable age biomarkers should also be optimized, a perfect system for the assessment of biological aging should be established, personalized interventions should be emphasized, and precise interventions should be advocated. The intrinsic links between the various aging drivers need to be focused on, multiple pathways need be combined to achieve anti-aging goals, and the right time to intervene needs to be determined immediately before the emergence of age-related diseases..."

Zhang Y, Wang X, Li W, et al. Intestinal microbiota: a new perspective on delaying aging? Front Microbiol. 2023;14:1268142.

 

I did not have time yet to dig into EPFL's paper but found this study which reportedly is the first to demonstrate a pure strain producing urolithins (but for urolithin A the authors also say other bacteria might be needed)

 

"...The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins...." (bold mine)

 

Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species.

http://www.ncbi.nlm....pubmed/24909569

 

The Gordonibacter bacteria taxonomy description is here:

http://www.ncbi.nlm....=Info&id=657308

 

Related and relevant to this thread is that "...The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice..."

http://www.ncbi.nlm....ubmed/15309440/

July 2024: The good story on UA is keeping going: https://doi.org/10.1...rr.2024.102406 

 Screenshot 2024-07-12 181616.png   1.11MB   0 downloads