273 replies to this topic

[albedo]

Another good read and list of references on probiotics supplementation on humans regarding the gut brain axis:

 

"...This review explores the evidence demonstrating how the gut microbiome may affect brain function in adults, thereby having an impact on
stress, anxiety, depression, and cognition. In vitro, in vivo, and human studies reporting an association between a change in the gut microbiome and functional changes in the brain are highlighted, as are studies outlining the mechanisms by which the brain affects the microbiome and the gastrointestinal tract. Possible modes of action to explain how the gut microbiome and the brain functionally affect each other are proposed. Supplemental probiotics to combat brain-related dysfunction offer a promising approach, provided future research elucidates their mode of action and possible side effects. Further studies are warranted to establish how pre- and probiotic interventions may help to balance brain function in healthy and diseased individuals..."

 

"...Communication between the brain and the microbiota involves epithelial receptor– mediated signaling, immune modulation, and stimulation of enteric neurons by bacterial metabolites. Important for this crosstalk is the ability of the microbiota to regulate the availability of circulating tryptophan, which affects serotonin synthesis, and to alter the expression of some CNS receptors, thereby enabling them to directly influence brain excitability and function as well as to exert epigenetic control of gene expression..."

 

Mohajeri MH, La fata G, Steinert RE, Weber P. Relationship between the gut microbiome and brain function. Nutr Rev. 2018

https://www.ncbi.nlm...pubmed/29701810

 

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[pamojja]

For anyone not aware yet, one can upload one's ubiome result to this private site: http://microbiomepre...rewebsites.net/

which is a huge data-base (in development), which for example identifies over- or undergrowth of particular bacteria and its food, supplemental or prescription modifier found reverences for.

Edited by pamojja, 26 May 2018 - 04:44 PM.

[albedo]

The following is an extremely interesting study on the longevity effect of acarbose (used to treat diabetes) mediated by the gut microbiota, even though there are obvious difficulties to translate to humans due to the vast variety of composition of microbiota between different organisms.

 

Changes in the gut microbiota and fermentation products associated with enhanced longevity in acarbose-treated mice.

“…We have demonstrated a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in thelongevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the microbiota illustrates the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, and to test a causal role of SCFAs in the observed effects of acarbose…”

https://www.biorxiv....311456.full.pdf

 

I am also puzzled by the fact that it is the second time I meet a drug, typically used for diabetes, investigated for lifespan or healthspan effects We know about metformin and his modulation of the human gut microbiota, e.g. increasing the population of Akkermansia muciniphila. We know about the potential beneficial effect of metformin on healthspan (possibly on longevity?) and I just speculate about this similitude maybe due to both drugs affecting morbidity and diabetes?

 

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[albedo]

A short small review on microbiota impact on health and longevity.

 

I found interesting the concept of functional core microbiome, the changes associated to age and dysbiosis, the emphasis on "biological age" vs. chronological age and the required homeostasis in the short fatty acid production. Also quoted are small molecules such as rapamycin and metformin.

 

Kim S, Jazwinski SM. The Gut Microbiota and Healthy Aging: A Mini-Review. Gerontology. 2018;:1-8.

 

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Edited by albedo, 30 July 2018 - 09:31 AM.

[albedo]

Insightful study, trying to meet some of the authors. Comments/questions?

 

"Dietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a host's microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patient's microbiota."

 

Gurry T, Gibbons SM, Nguyen LTT, et al. Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort. Sci Rep. 2018;8(1):12699.

 

[albedo]

I was just waiting for this to happen. Here is in my view a quite pioneering work on biological age determination using ML/AI on microbiota. The study is still at level or preprint as per today:

 

"...Our most accurate DNN regressor achieved the MAE of 3.94 years. This performance is comparable with the 1.9 MAE of the PhotoAgeClock, 2.7 of the state of art methylation aging clock, 7.8 MAE transcriptomic aging clock and 5.5 MAE of the hematological aging clock published previously. We also developed a method for microbiological feature selection and annotation..."

 

Quite fascinating is that: "...Interestingly, while it contains both beneficial (e.g. Bifidobacterium) and pathogenic (e.g. Pseudomonas aeruginosa) microbes, seno-positive or seno-negative status is not determined by the nature of host-microbe interactions (Figure 12)..."

 

Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects

Fedor Galkin, Alexander Aliper, Evgeny Putin, Igor Kuznetsov, Vadim N Gladyshev, Alex Zhavoronkov

bioRxiv 507780; doi: https://doi.org/10.1101/507780

[albedo]

Interesting study including casual relationships made on humans with normal glycemic levels looking at the SCFA impact on metabolic diseases risks and finding different roles between butyrate and propionate:

 

"Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity¹. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available², then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality³, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10⁻⁵), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings."

 

Sanna S, Van zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019;

[albedo]

A company to follow on Akkermansia muciniphila (sorry if old news to you)

University of Louvain and Wageningen University launch their new spin-off A-Mansia: a microbiome company

https://uclouvain.be...in-off-ucl.html

 

[albedo]

Good review of the current thinking about the relationship between aging and the host microbiota:

https://www.leafscie...binar-released/

[albedo]

I am always concerned by heavy usage of computer screen for my vision. This is an encouraging research which hopefully will became replicated and actionable in the future:

Morita Y, Jounai K, Miyake M, Inaba M, Kanauchi O. Effect of Heat-Killed Lactobacillus paracasei KW3110 Ingestion on Ocular Disorders Caused by Visual Display Terminal (VDT) Loads: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study. Nutrients. 2018;10(8)

"...In conclusion, the findings of this study indicated that L. paracasei KW3110 suppressed blue light-induced retinal pigment epithelial cell death in vitro and ingestion of L. paracasei KW3110 had positive effects for improving some objective and subjective parameters of eye disorders and eye fatigue induced by VDT loads. Further studies enrolling many more subjects should be carried out to more clearly reveal the clinical effects of L. paracasei KW3110 on ocular disorder including eye fatigue..."

Not a huge surprise considering the gut/brain axis and the fact some consider eyes as a part of the brain. What do you do to protect your eyes?

Edited by albedo, 04 July 2019 - 12:31 PM.

[albedo]

Interesting results on health and life spans, on mouse models and human progeria patients, in particular about the positive role of Akkermansia muciniphila:

 

Bárcena C, Valdés-mas R, Mayoral P, et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat Med. 2019

 

The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways^1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer^3-6, but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.

[albedo]

Interesting video by Dr Greger on microbiota enterotype where "There appear to be just two types of people in the world: those who have mostly Bacteroides type bacteria in their gut, and those whose colons are overwhelmingly home to Prevotella species instead."

https://nutritionfac..._eid=f56b67bcfa

[albedo]

Scientists in global project to create world's largest human microbiome database

https://www.nutraing...X8FZ7w0m5mR&p2=

[albedo]

Additional evidence to keep your Vitamin K in check and its link to gut microbiota and diet. Not only for coagulation and calcium delivery to bones but also for the brain:

Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults

https://www.ncbi.nlm...pubmed/31518386

"...This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition..."

 

[albedo]

Increasing evidence and elegant experiments on impact of gut microbiota on cognition and typical metabolic aging signaling such as mTOR, AMPK and SIRT1. Noticeably beneficial impact reproduced by butyrate oral administration.

 

"The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota–derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients."

Kundu P, Lee HU, Garcia-perez I, et al. Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice. Sci Transl Med. 2019;11(518)

 

"The process of aging underlies many degenerative disorders that arise in the living body, including gradual neuronal loss of the hippocampus that often leads to decline in both memory and cognition. Recent evidence has shown a significant connection between gut microbiota and brain function, as butyrate production by microorganisms is believed to activate the secretion of brain-derived neurotrophic factor (BDNF). To investigate whether modification of intestinal microbiota could impact cognitive decline in the aging brain, Romo-Araiza et al. conducted a study to test how probiotic and prebiotic supplementation impacted spatial and associative memory in middle-aged rats. Their results showed that rats supplemented with the symbiotic (both probiotic and prebiotic) treatment performed significantly better than other groups in the spatial memory test, though not in that of associative memory. Their data also reported that this improvement correlated with increased levels of BDNF, decreased levels of pro-inflammatory cytokines, and better electrophysiological outcomes in the hippocampi of the symbiotic group. Thus, the results indicated that the progression of cognitive impairment is indeed affected by changes in microbiota induced by probiotics and prebiotics. Potential future applications of these findings center around combatting neurodegeneration and inflammation associated not only with aging but also with the damaging posttraumatic effects of ischemic stroke."

Heyck M, Ibarra A. Microbiota and memory: A symbiotic therapy to counter cognitive decline?. Brain Circ. 2019;5(3):124-129.

 

 

 

[albedo]

It might be useful to log this study also here; it focuses on the two-way exchange gut microbiota-brain in health and disease:

 

Pluta R, Ułamek-Kozioł M, Januszewski S, Czuczwar SJ. Gut microbiota and pro/prebiotics in Alzheimer’s disease. Aging (Albany NY). 2020; . https://doi.org/10.18632/aging.102930 [Epub ahead of print]

 

"...We should emphasize with a high probability that bacteria and fungi from the intestines can cause neuroinflammation and autoimmune reactions during the aging and Alzheimer’s disease development. A significant decline in cognitive function was confirmed in microbial transplanted mice from patients with Alzheimer’s disease relative to age. Regression analysis showed a relationship between cognitive decline and age of microflora transplanted mice from sick individuals. This directly proves that microflora transplanted mice from diseased patients had reduced cognitive function as recipients. Therefore, it has been suggested that the gut microflora affects the behavior of the host through its own metabolites. There is no doubt that in Alzheimer’s disease patients attempts to restore the gut microbiome to the boost composition in healthy adults can significantly slow the progression of neurodegeneration by reducing amyloidogenesis and/or neuroinflammation...."

[William Sterog]

Thanks for keeping this alive, Albedo. I really appreciate your effort.

[albedo]

This review contains information likely known to most of you but thought to log it here anyway. The review was submitted and accepted by the Microbiome in Health and Disease section of the Journal Frontiers in Cellular and Infection Microbiology. I find it useful to the extent it focuses on cognition covering aspects such as oral next to the gut microbione, lifestyle, circadian, mechanistic aspects, chronic noise, interventions, ... all grouped in a single paper, so the reference list is quite extensive and useful:

 

Askarova S, Umbayev B, Masoud AR, et al. The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease. Front Cell Infect Microbiol. 2020;10:104.

 

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(edit: spelling)

Edited by albedo, 23 April 2020 - 12:13 PM.

[albedo]

Ou, Z., Deng, L., Lu, Z. et al. Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer’s disease. Nutr. Diabetes 10, 12 (2020).

https://doi.org/10.1...1387-020-0115-8

"...Akk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD..."

Any status on a possible probiotics formulation? They also cite a study on possible role of metformin.

[albedo]

Good coverage of the results of the large PREDICT study (Tim Spector) now published in Nature Medicine:

https://www.nutraing...ion-revelations

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https://www.nutraing...-the-microbiome

 

"Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies"

https://www.nature.c...1591-020-0934-0

 

(edit: correcting link)

Edited by albedo, 14 June 2020 - 09:35 AM.

[albedo]

Viome launches world’s first at-home service to measure and improve immunity, inflammation, gut health and aging

https://www.globenew...-and-aging.html

Looks quite comprehensive. The test is based on a technology described in a paper not yet published though (on BioRxiv). Interesting ..

[albedo]

Another innovation on prebiotics from carrots and Belgium:

https://www.nutraing...ign=29-Jun-2020

[rodentman]

Viome launches world’s first at-home service to measure and improve immunity, inflammation, gut health and aging

https://www.globenew...-and-aging.html

Looks quite comprehensive. The test is based on a technology described in a paper not yet published though (on BioRxiv). Interesting ..

 

 

Thanks for this.  I am considering taking the new 'GI 360 Stool Analysis Fecal Test' offered by life extension.  It's here: https://www.lifeexte...ysis-fecal-test

 

I'm not an expert on any of this.  How would this compare to the Viome, health intelligence and gut intelligence tests?

[albedo]

Thanks for this.  I am considering taking the new 'GI 360 Stool Analysis Fecal Test' offered by life extension.  It's here: https://www.lifeexte...ysis-fecal-test

 

I'm not an expert on any of this.  How would this compare to the Viome, health intelligence and gut intelligence tests?

I am no expert either, unfortunately, and never carried a comparison so cannot talk by direct experience. While Viome announcement is very interesting I think we should wait how it pans in terms of the platform they are developing: "This test, along with the previously published stool metatranscriptome test and upcoming saliva and vaginal metatranscriptome tests, can be integrated into a comprehensive systems biology platform that can be applied to population-scale longitudinal studies. Such large studies will identify mechanisms of chronic disease onset and progression, improve or bring new diagnostic and companion diagnostic tools, and enable precision nutrition (including probiotics) and microbiome engineering to prevent and cure chronic diseases."

LEF test seems to me a good base to start with. I would definitively have taken it if I was in US. A conceptual issue I have with all these tests is on the market is both with actionability of what you found and clinical validation. E.g. how you define a reference population? The latter is challenging even for tests which by far have a better validation such as blood tests. Even there you have challenges as for example a stratification by age group etc ...

I would be very curious if you decide for one of these test and can share experience. Thank you.

 

[pamojja]

I would be very curious if you decide for one of these test and can share experience. Thank you.

 

At https://microbiomepr...tgun-providers/ you find someone reeviewing them. Who used available microbiome testing to improve his main condition, ME/CFS.
 

[rodentman]

At https://microbiomepr...tgun-providers/ you find someone reeviewing them. Who used available microbiome testing to improve his main condition, ME/CFS.
 

 

 

Thanks.  I think he is currently using thryve.  I am not sure which service to use.  I feel like I would prefer LEF, just based on reputation, but I don't know exactly what to look for.  I was looking at the LEF GI360 report sample here: file:///C:/1W/tmpdwnld/LC100088_Sample_GI360.pdf , and I don't understand how to properly interpret it.

 

I have both CFS and Crohn's so I am sure my microbiome is less than optimal.  In general, I've noticed overall improvements when I get most of my fat/protein calories from yogurt.  It's nothing special/fancy, just Fage/Chobani greek yogurt, so I assume there is some probiotic that is helping me.  I've noticed outrageously expensive yogurt starter cultures, like Bravo (the one that Sinclair takes), which is $50.00, but I'd be hesitant to spend that much unless I knew more about it's benefits.

[pamojja]

Thanks.  I think he is currently using thryve.  I am not sure which service to use.  I feel like I would prefer LEF, just based on reputation, but I don't know exactly what to look for.  I was looking at the LEF GI360 report sample here: file:///C:/1W/tmpdwnld/LC100088_Sample_GI360.pdf , and I don't understand how to properly interpret it.

 

I have both CFS and Crohn's so I am sure my microbiome is less than optimal.  In general, I've noticed overall improvements when I get most of my fat/protein calories from yogurt.  It's nothing special/fancy, just Fage/Chobani greek yogurt, so I assume there is some probiotic that is helping me.  I've noticed outrageously expensive yogurt starter cultures, like Bravo (the one that Sinclair takes), which is $50.00, but I'd be hesitant to spend that much unless I knew more about it's benefits.

 

Here it is on the web: https://www.lifeexte...ample_gi360.pdf

 

Just about 50 bacteria tested for - not giving their real numbers - forget this test. Its utterly useless. For example my ubiome (when still available) already found above 240 different bacteria with exact percentage given: https://docs.google....#gid=1806806580

 

How they even can consider diversity, if only a few are tested for? Some untouched hunter gatherers still have up to 2000 different gut bacteria!
 

Since the demise of ubiome thryve seems to be the best deal. See example interpretation (for free):

 

What do you want to do today?

 

Tell me why I may want to modify my microbiome

 

Tests

• I want to see what I may get before I decide to upload my sample. Goto login and use "Demo" with Sample Id:"1234567"

 

Here again: http://microbiomepre....com/home/logon

Edited by pamojja, 30 June 2020 - 08:17 PM.

[rodentman]

Here it is on the web: https://www.lifeexte...ample_gi360.pdf

 

Just about 50 bacteria tested for - not giving their real numbers - forget this test. Its utterly useless. For example my ubiome (when still available) already found above 240 different bacteria with exact percentage given: https://docs.google....#gid=1806806580

 

How they even can consider diversity, if only a few are tested for? Some untouched hunter gatherers still have up to 2000 different gut bacteria!
 

Since the demise of ubiome thryve seems to be the best deal. See example interpretation (for free):

 

 

Here again: http://microbiomepre....com/home/logon

 

Thanks.  I went ahead and ordered the thryve.  It's cheap enough ($100 after wethrift.com coupon) that I can get it done multiple times, which I've heard is important, since I've read the microbiome can change quite a bit in a short period of time.

 

I'll definitely use the microbiomeprescription.com site, and will also try the http://aging.ai/floro-clock/#form_inp  just for kicks.

[albedo]

Thank you Pamojja for all these information. You obviously have done your home work! Very useful when I will decide to make my own test. My only baseline microbiology stool tests were made at Genova Diagnostics loooong ago (2006 and 2011) so I would like to have a more sophisticated and current analysis.

[albedo]

No time to read now in full, but it looks interesting:

 

https://www.nutraing...ign=11-Aug-2020

 

Xiao, Y., Angulo, M.T., Lao, S. et al. An ecological framework to understand the efficacy of fecal microbiota transplantation. Nat Commun 11, 3329 (2020). https://doi.org/10.1...467-020-17180-x

https://www.nature.c...-17180-x#citeas