Welcome to the Human Microbiome wiki!
Short link to this page: HumanMicrobiome.info
On this page:
- Antimicrobial peptides
Blog: Understanding Microbiome Research: https://microbiomethod.blogspot.co.uk/
Researcher Elisabeth Bik's list of other sources of microbiome info: https://microbiomedigest.com/microbiome-papers-collection/microbiome-blogs-tweeps-and-books/
Some of 2016's most discussed research papers: https://microbiomedigest.com/2016/12/21/vote-for-the-best-microbiome-papers-of-2016/ | Same for 2017: https://microbiomedigest.com/2017/12/26/vote-for-the-best-microbiome-papers-of-2017/ - https://microbiomedigest.com/2018/01/02/the-best-microbiome-papers-of-2017/
Use PubPeer's browser addon to see peer discussions of academic publications: https://pubpeer.com/static/faq#29
Do NOT eat dirt .
Things which are detrimental:
Advanced glycation end products (AGEs) .
Alcohol: Generally . Chronic vapour alcohol exposure . Acute-on-chronic alcohol . Detrimental to mouth microbiome . Alcohol induced alterations of the microbiome may explain reward-seeking behaviors as well as anxiety, depression, and craving in withdrawal and increase the risk of developing psychiatric disorders . Increases susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis . Aug 2019 systematic review and meta-analysis.
Antibiotics (see abx section below).
Food additives . Emulsifiers . Soy lecithin . Sulfites . Glycerol Monolaurate . Trehalose (sugar additive) . Carrageenan and carboxymethylcellulose (CMC) . CMC and polysorbate 80 (P80) . Titanium dioxide .
Insecticides: aldicarb .
Mercury: Acute oral methylmercury, Jan 2020, rats.
Perfluorooctane sulfonate (PFOS): Jan 2020, mice.
Tobacco: Smoking dokha .
Trans fats .
Tributyltin (TBT) .
IV vs oral, which is more harmful: https://archive.is/9QV89
Many studies showing long-term damage: http://HumanMicrobiome.wiki/Intro#more-effects-of-antibiotics
Non-antibiotic drugs promote antibiotic resistance. These accidental bactericides included proton-pump inhibitors such as omeprazole, calcium-channel blockers, antihistamines, painkillers and antipsychotics. (2018): https://archive.fo/VrGM7
More via "antibiotics" flair in sidebar: https://old.reddit.com/r/humanmicrobiome/search?q=flair%3A%27Antibiotics%27&sort=new&restrict_sr=on
Why your doctor’s advice to take all your antibiotics may be wrong: https://archive.fo/qikfW
Shorter (7 day vs 14 day), tailored antibiotic regimens shown effective at treating bacterial infections. 14 day regimens seem to be based on medical tradition rather than on sound scientific evidence (Jun 2020, n=504 adults) https://archive.vn/YRbzO
In a lab, researchers created three new antibiotics that kill C. difficile by preventing the expression of bacterial genes that are important for its survival. This approach — called antisense therapy — allows the drug to kill only C. difficile, unlike many antibiotics that kill multiple forms of bacteria. (2018): http://news.psu.edu/story/523890/2018/06/06/research/killing-bacteria-silencing-genes-may-be-alternative-antibiotics
Peptides are created by gut bacteria, as well as by eukaryotic hosts during symbiotic interactions with bacteria.
AMPs are involved in aging: http://HumanMicrobiome.info/aging#Peptides
Antimicrobial Peptides Vs. Antibiotics: http://biorxiv.org/content/early/2017/05/23/138107
Spider peptides battle superbugs and cancer - Gomesin, an antimicrobial peptide (AMP) from a spider, can function as an antibiotic, and it also has anticancer activity. Australian scientists synthesized new versions that were 10 times better at killing most bacteria than previously reported: https://www.acs.org/content/acs/en/pressroom/presspacs/2017/acs-presspac-august-9-2017/spider-peptides-battle-superbugs-and-cancer.html
Review, 2018: Role of antimicrobial peptides in controlling symbiotic bacterial populations: https://sci-hub.tw/http://pubs.rsc.org/en/Content/ArticleLanding/2018/NP/C7NP00056A#!divAbstract
"What we eat becomes who we are."
Impacts & limitations:
These studies explain the impacts and limitations of diet on shaping the gut microbiome:
In short, diet changes the percentages of microbes already there, based on which microbes thrive most on what you're feeding them. And diet changes what metabolites are created, but generally does not change the fundamental make up of the gut microbiome. To change it fundamentally would require adding/subtracting microbes via interventions like FMT, antimicrobials, and possibly probiotics. Though long-term starvation of microbial populations via absence of dietary components such as fiber, can result in extinctions that persist and compound over generations.
Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome (2016): http://www.nature.com/articles/nmicrobiol2016221
Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight (Mar 2020, n=49) https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqaa046/5809430
Macronutrient differences impact western gut microbiome, but not Hadza gut microbiomes (Jeff Leach 2018): https://youtu.be/tjLW_DaQ9qI?t=2305
Diabetes-Associated Alterations in the Cecal Microbiome and Metabolome are Independent of Diet or Environment in the UC Davis Type 2-Diabetes Mellitus Rat Model (2018): https://www.physiology.org/doi/abs/10.1152/ajpendo.00203.2018
Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet (mice, 2018): https://dx.doi.org/10.1155%2F2018%2F3462092
Diet matters less than evolutionary relationships in shaping gut microbiome. Study is the largest published comparative dataset of non-human primate gut microbiomes to date. https://www.eurekalert.org/pub_releases/2018-07/nu-dml073018.php | Evolutionary trends in host physiology outweigh dietary niche in structuring primate gut microbiomes (2018): https://www.nature.com/articles/s41396-018-0175-0
Diet-induced extinctions in the gut microbiota compound over generations (2016): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850918 - but reintroducing the food (fiber in this instance) does not return the microbes.
"So why can’t we supplement our diet with short-chain fatty acids? The ecosystem that produces the acids may be as important as the acids themselves. Trials testing prebiotics: only individuals who already harbored a baseline diversity benefited from these dietary interventions. Those whose microbial communities were too impoverished didn’t—or couldn’t—respond to the new diet. They seemed to lack the ability. You can eat all the fiber you want (unless your food is contaminated with feces) and you’ll never re-acquire microbes like H. pylori. The only way to restore such microbes may be to deliberately reintroduce them." http://nautil.us//issue/30/identity/how-the-western-diet-has-derailed-our-evolution
Same phenomena in packrats: Woodrats lost their ability to eat toxic creosote bushes after antibiotics killed their gut microbes. Woodrats that never ate the plants were able to do so after receiving fecal transplants with microbes from creosote-eaters https://archive.unews.utah.edu/news_releases/fecal-transplants-let-packrats-eat-poison/
Anti-inflammatory effects of a dietary intervention were not related to changes in gut microbiota composition during the intervention, but were correlated with microbiota composition at baseline (2018): https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0381-7 "Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: a randomized controlled trial."
"effects of individual differences outweighed the effect of experimental diets" https://doi.org/10.1128/mBio.01604-18
Diet can impact bacteria's phage production .
Influence of short-term changes in dietary sulfur on the relative abundances of intestinal sulfate-reducing bacteria (Feb 2019): https://doi.org/10.1080/19490976.2018.1559682 "we could not detect a change with dietary treatments. These observations are consistent with re-analysis of two previously published dietary intervention studies"
Review, 2020: Current explorations of nutrition and the gut microbiome: a comprehensive evaluation of the review literature https://doi.org/10.1093/nutrit/nuz106
Review, 2017: Gut microbiota functions: metabolism of nutrients and other food components: https://link.springer.com/article/10.1007%2Fs00394-017-1445-8).
Review, 2018: Mechanisms by which gut microorganisms influence food sensitivities https://www.nature.com/articles/s41575-018-0064-z
Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome (2019): https://www.pnas.org/content/116/9/3688 "suggesting that diet may be directly regulating innate immunity"
Resistant starches can be a powerful tool.
The role of short-chain fatty acids, by Jun Kim Ph.D.
Fiber intake is associated with gut microbial diversity, and gut microbial diversity is generally good. So a variety of whole, fibrous foods from legumes, fruits, and vegetables (including root veg) is generally recommended. However, since fiber feeds a broad range of microbes it can feed problematic ones as well. Thus "person to person variation" reigns supreme. One study showed that removing fiber from the diet improved all constipation symptoms and increased BM frequency!
Iron may be feeding pathogens in some people. Experiment with removing iron rich foods/supplements from your diet.
Whole food > processed:
Gut microbiota and systemic inflammation changes after bread consumption. Systemic inflammation was only detected after industrial bread consumption. Healthy bread properties seem to depend on its ingredients and manufacture process .
Variation from person to person:
There is a very significant variation from person to person (depending on their unique gut microbiome) regarding reactions to "generally healthy" foods. So you should definitely experiment for yourself and not force something that makes you feel worse but is very healthy for most other people .
One-size-fits-all is a size that fits no one. Excerpts from the foreword from the book "Primal Body, Primal Mind".
Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to High Fructose Consumption in Mice (2018): https://doi.org/10.1101/439786
Review, 2018: The Effect of Gluten-Free Diet on Health and the Gut Microbiota Cannot Be Extrapolated from One Population to Others https://www.mdpi.com/2072-6643/10/10/1421/htm "This argument is primarily based on the highly individualized pattern of gut microbial composition and metabolic activity in each person, the variability of the gut microbiota over time and the plethora of factors associated with this variation"
TMAO is a bacterial metabolite linked to heart disease. It is produced by gut bacteria after eating meat (dietary l-carnitine). But vegetarians can lack the bacteria that make TMAO, so their levels don't increase after eating meat. The same effect can be reproduced using antibiotics. http://stm.sciencemag.org/content/5/183/183ec75
Bacterial community response to cruciferous vegetables was individual-specific (2009): Human Gut Bacterial Communities Are Altered by Addition of Cruciferous Vegetables to a Controlled Fruit- and Vegetable-Free Diet https://academic.oup.com/jn/article/139/9/1685/4670531
"In the human study, two distinct and inverse responses to tart cherry consumption were associated with initial levels of Bacteroides" (2018): https://www.sciencedirect.com/science/article/pii/S0955286317307143
Elimination diets are extremely useful to figure out exactly what is good and bad for you. Establish a baseline by starting out with a liquid (milk, 100% fruit/vegetable juice, broth, water, etc.) you know you tolerate well, then add in one food at a time to see how it makes you feel. Do not ignore the impact of spices when doing this! Many of them are officially prebiotics, and nearly all of them have phytochemicals like antioxidants, flavonoids, carotenoids, and polyphenols, which either feed bacteria or cause specific shifts in the gut microbiome that may be beneficial/detrimental to various people.
Keto, carnivore, and 80/10/10 are all types of elimination diets.
Be extremely skeptical of suggestions that detrimental impacts are actually a good thing because they represent "die off/herx". This is probably one of the top most widespread & dangerous pieces of misinformation. If you are not seeing significant improvements from baseline after dipping below baseline from a hypothesized bad reaction from harmful microbes dying off, then you are likely simply harming yourself. Any genuine herx reaction should also be very temporary (1-2 days).
Protein & fat:
Review, 2016: Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin https://www.sciencedirect.com/science/article/abs/pii/S0924224416303612
Worse inflammatory profile in omnivores than in vegetarians associates with the gut microbiota composition: https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-017-0261-x
In general, fermentation metabolites from carbohydrates and associated phenolic compounds have beneficial effects; by the contrary protein derived fermentation products are detrimental for health .
There's a big difference between types/sources of fats & proteins . The body processes them differently, thus they have very different impacts on weight and gut microbiome. Soy oil vs coconut oil.
Dietary protein sources differentially affect microbiota, mTOR activity and transcription of mTOR signaling pathways in the small intestine [mice]. 2018 review: "effects of high protein diet on the gut were dependent on the protein source (i.e. from plant or animal sources)" https://doi.org/10.1016/j.clnu.2018.09.016
Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice (Oct 2019) https://www.biorxiv.org/content/10.1101/819979v1.abstract "Our results demonstrate a dominant ecological and physiological role of bacteria in gut microbiomes, but highlight fungi as an ecological factor shaping the assembly of the bacterial community and a direct capacity to impact immune system and modulate disease susceptibility"
Probiotic yeast may offer an effective treatment for drug-resistant fungal infections. Study shows that yeasts derived from food are effective in preventing infections and reducing the virulence of several Candida species https://www.eurekalert.org/pub_releases/2019-12/wpi-pym121019.php. Probiotic Yeasts Inhibit Virulence of Non-albicans Candida Species (Oct 2019).
Current limitations and unknowns are extreme. There are a plethora of microbes which are either unknown and/or not tested for currently. 16s only tests for bacteria, and not down to the strain level, which is of vital importance.
This recent study for example, showing one bacterial strain inducing liver damage (2018): http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0198262 - That kind of thing is absolutely not tested for with either conventional, or 16s commercial testing.
Till mid 2016 they were only able to culture an estimated 1% of gut microbes: https://archive.is/JnStd – http://www.nature.com/nature/journal/v533/n7604/full/nature17645.html
Only 35 to 65% of molecular species detected by sequencing have representative strains in culture (Apr 2017): http://www.tandfonline.com/doi/full/10.1080/19490976.2017.1320468
Using advanced metagenomics techniques, researchers have found that conventional culture-based lab tests may misdiagnose as many as half of the microbial causes of diarrheal diseases in children (Nov 2019) https://rh.gatech.edu/news/629100/metagenomics-unlocks-unknowns-diarrheal-disease-cases-children
8/21/2017 Stanford study using shotgun sequencing says we still don't know 99% of human microbes: https://archive.is/wgucb
9/16/2017 From an international database of more than 1,500 metagenomes, the UQ team reconstructed the individual genomes of 7,280 new bacteria and 623 new archaea. Of these microorganisms, roughly a third were unlike anything scientists had seen before, warranting the creation of 17 new bacterial phylums and three new achaeal phylums. https://futurism.com/scientists-just-discovered-organisms-that-are-distinct-from-any-life-forms-known-to-science/
10/2/2017 NIH Microbiome Project Triples Number of Previously Identified Bacterial Genes: https://www.genengnews.com/gen-news-highlights/nih-microbiome-project-triples-number-of-previously-identified-bacterial-genes/81255000
3/19/2018 Researchers have used artificial intelligence (AI) to discover nearly 6,000 previously unknown species of virus https://www.nature.com/articles/d41586-018-03358-3
3/21/2018 Sanguibacter massiliensis sp. nov., Actinomyces minihominis sp. nov., Clostridium minihomine sp. nov., Neobittarella massiliensis gen. nov., and Miniphocibacter massiliensis gen. nov., new bacterial species isolated by culturomics from human stool samples https://www.sciencedirect.com/science/article/pii/S2052297518300222
4/4/2018 Researchers have discovered more than 200 previously unknown viruses in a category whose members cause illnesses such as influenza and haemorrhagic fevers. https://www.nature.com/articles/d41586-018-04102-7
4/30/2018: About half of all oral bacteria are uncultivable https://www.frontiersin.org/articles/10.3389/fphys.2018.00342/full
1-Mar-2018: How reliable is diagnostic testing for Zika? Almost two thirds of all laboratories showed false-positive or false-negative results. https://www.eurekalert.org/pub_releases/2018-03/gcfi-hri030118.php
1/17/2019: Thousands Of New Microbiome Species Found Living on the Human Body. The researchers estimate one of the new species is the seventh most prevalent intestinal microbe in the human microbiome http://blogs.discovermagazine.com/d-brief/2019/01/17/population-human-microbiome-new-species-western
2/04/2019: More than 100 new gut bacteria discovered in human microbiome https://www.sciencedaily.com/releases/2019/02/190204114602.htm. A human gut bacterial genome and culture collection for improved metagenomic analyses https://www.nature.com/articles/s41587-018-0009-7
2/11/2019: Almost 2000 unknown bacteria discovered in the human gut https://www.ebi.ac.uk/about/news/press-releases/2000-unknown-gut-bacteria-discovered. A new genomic blueprint of the human gut microbiota https://www.nature.com/articles/s41586-019-0965-1
2/11/2019: "Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach" https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00034/full
2/27/2019: "Current gold standard sequencing procedures do not permit the determination of taxa abundances per gram of stool, but only provide proportional information on the fraction of the microbiota belonging to a particular genus in the sequenced library. Changes in total microbial density in faecal samples might be a key feature of a dysbiotic ecosystem and therefore a crucial element in microbiome-based diagnostics. Amplicon sequencing provides no information on metabolic potential, and library preparation biases exaggerate the relative abundance of dominant taxa" https://www.tandfonline.com/doi/full/10.1080/17843286.2019.1583782
"It's not enough to study the composition, or the increase or decrease of a species. We also have to understand how the microbiota sense us, and how they change their 'behavior' accordingly." (May 2019) https://www.eurekalert.org/pub_releases/2019-05/asfm-hsb051019.php
8/14/2019: Research conducted by scientists from Harvard Medical School and Joslin Diabetes Center uncovered a "staggering microbial gene diversity". More than half of the bacterial genes examined occurred only once (called “singletons”) and were specific to each individual https://hms.harvard.edu/news/microbial-fingerprinting
Current (2018) commercial testing (16s) has very limited value. Here's a great write up by a microbiologist about it. More:  - including commentary from Rob Knight and others. A real life example. Another researcher/professor in the field agreeing. Excellent podcast that supports and gets into the details.
A major factor is also that most testing is only for bacteria, but it's looking like phages might be more important. There's also fungi and archaea.
Nonsensical results like this are common. And these two studies  explain why. Essentially, many people's stools are not uniform, thus depending on which part of the stool you sample, you'll get different results. Thus homogenizing the stool prior to sampling will give more consistent results, but also changes the proportions of the results. This is likely a major problem with uBiome for instance, who use a swab method rather than whole stool.
Various companies that do it: ubiome, genova, American Gut, viome, uBiota, biocollective, doctor's data, bioscreen. Here's a comparison of the different microbes each test for.
Here's an example report from BioScreen, which goes through a doctor and seems a little more useful.
Here's an example report from Biocollective.com.
Example report from Genova's GI Effects.
Example report from Diagnostic Solutions GI Map: https://www.diagnosticsolutionslab.com/sites/default/files/GI-MAP-Sample-Report_ARs.pdf - this one seems very useful.
Directlabs.com has a variety of tests: https://www.directlabs.com/pop/OrderTests/tabid/35269/language/en-US/Default.aspx - The "Comprehensive Digestive Stool Analysis 2.0™ (CDSA 2.0)-Genova Kit" is probably the most useful one from them.
This is essentially the best input you can expect to get from sharing your results.
The Intestinal Virome and Immunity (2018): https://doi.org/10.4049/jimmunol.1800631
Review, 2018: Beyond Bacteria: Bacteriophage-Eukaryotic Host Interactions Reveal Emerging Paradigms of Health and Disease https://www.frontiersin.org/articles/10.3389/fmicb.2018.01394/full - "Phages may be naturally internalized into eukaryotic cells. As phages are significant reservoirs of genetic diversity and considering phages are capable of entering eukaryotic cells, this raises questions about the possibility of bidirectional trans-kingdom gene exchange between phages and their animal hosts."
Potential for harm: Review, 2018: Bacteriophages as New Human Viral Pathogens: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027513/ "We suggest that bacterial viruses have different ways to directly and indirectly interact with eukaryotic cells and proteins, leading to human diseases"
Review, June 2019: What is (not) known about the dynamics of the human gut virome in health and disease https://www.sciencedirect.com/science/article/pii/S1879625719300173
Review, June 2019: Phage Therapy in the Twenty-First Century: Facing the Decline of The Antibiotic Era; Is it Finally Time for The Age of the Phage? https://www.annualreviews.org/doi/10.1146/annurev-micro-090817-062535
Review, 2017: Phages in the Human Body: http://journal.frontiersin.org/article/10.3389/fmicb.2017.00566/full
Review, 2017: Bacteriophages in the human gut: our fellow travelers throughout life and potential biomarkers of heath or disease. Phages are the largest part of the human microbiome: http://www.sciencedirect.com/science/article/pii/S0168170217302149
Review, 2017: The human intestinal virome in health and disease: http://onlinelibrary.wiley.com/doi/10.1111/apt.14280/full
Review, 2017: Bacteriophages in the gastrointestinal tract and their implications: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553654/
Phages vs antibiotics: "The upside and downside to using phage therapy is that the viruses are extremely specific. The upside is that phage will only kill a very specific type of bacterium, whereas antibiotics lay waste to many different bacteria, including friendly ones. The downside is that the phage are too specific."
Addressing superbug resistance with phage therapy. "The study is significant because it is the first time bacteriophage therapy has been used in the USA to treat a patient who had an antibiotic-resistant, blood stream infection." (Aug 2017) https://medicalxpress.com/news/2017-08-superbug-resistance-phage-therapy.html
Great article on the current (Nov 2017) status in the US of the use of phages for fighting an infectious disease: http://www.cidrap.umn.edu/news-perspective/2017/11/save-life-doctors-turn-bacteria-killing-viruses | Another from Nov 2017 about a separate occurrence: https://www.statnews.com/2017/11/28/phage-therapy-mallory-smith/ | Another from Dec 2017: https://motherboard.vice.com/en_us/article/9kdbqa/bacteriophages-phage-therapy-antibiotic-resistant-bacteria (the video on the page has even more).
Phages are an important component of FMT success .
Transferring just the bacteriophage was sufficient to reduce resting metabolic rate and cause weight gain in control mice (2015): https://www.sciencedaily.com/releases/2015/12/151214130811.htm
The Virus That Could Cure Alzheimer’s, Parkinson’s, and More: http://www.pbs.org/wgbh/nova/next/body/phage-alzheimers-cure/
Phage therapy via clinics ($1k-4k) or supplements ($30-200) - link.
Phage supplements in the US: https://archive.fo/hF4y8#selection-789.0-789.1