Diet and the Microbiome
The impacts and limitations of diet in shaping the gut microbiome. Our unique, individualized microbiomes determine the best foods for us.
"What we eat becomes who we are."
Review, 2022: Rethinking healthy eating in light of the gut microbiome https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(22)00222-0
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
Gut immune cells respond directly to nutrients (Apr 2021) https://web.archive.org/web/20221129075753/https://old.reddit.com/r/HumanMicrobiome/comments/mmojt4/mysterious_immune_cells_change_the_gut_lining_to/
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 intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood (Jan 2021, n=128) https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqaa340/6104796
Study finds childhood diet has lifelong impact (Jan 2021, mice) https://www.eurekalert.org/pub_releases/2021-02/uoc--sfc020221.php
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
Many koalas could only eat certain species of eucalyptus. But after FMT from other koalas who were able to eat other species, it allowed them to also digest it [2018], [2019].
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."
Benefits of fasting, the ketogenic diet, and other dietary interventions, are dependent on the gut microbiome, and the benefits can be transferred via FMT [1][2][3][4][5][6].
"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 [1].
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"
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[1][2][3][4][5][6]. However, since fiber feeds a broad range of microbes it can feed problematic ones as well. Thus "person to person variation" reigns supreme [1]. One study showed that removing fiber from the diet improved all constipation symptoms and increased BM frequency[1]!
Iron may be feeding pathogens in some people [1][2][3]. Experiment with removing iron rich foods/supplements from your diet.
See also https://humanmicrobiome.info/prebiotics and "obesity & diet" section of the intro page: https://humanmicrobiome.info/intro#obesity--diet
Whole food > processed:
Purified/processed fibers are not adequate (in regards to protecting mucus barrier)[1,2,3]. And supplementing a low fiber/carb diet with prebiotics can actually have detrimental affects[1].
Whole grains > brans & refined grains [1][2].
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 [1].
Variation from person to person:
There is 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 [1][2][3][4][5][6][7][8].
One-size-fits-all is a size that fits no one. Excerpts from the foreword from the book "Primal Body, Primal Mind".
What you eat will protect you from flu — but only if you have the right gut bacteria.
Should you eat more dietary fiber? New study says it depends (Jun 2024, n=59) https://forum.humanmicrobiome.info/threads/should-you-eat-more-dietary-fiber-new-study-says-it-depends-jun-2024-n.451/ Gut microbial features and dietary fiber intake predict gut microbiota response to resistant starch supplementation. Another similar one a few months later.
BBC Two: firm links between a person’s individual response to food, and to the gut bacteria that they have. Study
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
Age is an important factor in this variation of responses to diet [1][2][3]. As is sex [1].
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 shortly 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).
Elimination diets:
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.
Fasting:
The benefits of fasting, the ketogenic diet, and other dietary interventions, are dependent on the gut microbiome, and the benefits can be transferred via FMT [1][2][3][4][5][6].
Numerous calorie restriction studies implicating changes in the gut microbiome as a causative factor:
Transplantation of fecal microbiota, from normal mice on Fasting Mimicking Diet (FMD) to antibiotic-pretreated Parkinson’s Disease (PD) mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD (Feb 2019) https://link.springer.com/article/10.1007%2Fs13311-019-00719-2 Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites.
Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment (Feb 2020, mice) https://www.nature.com/articles/s41467-020-14676-4
Vegan-based fasting diet reduces inflammatory bowel disease pathology in mice. Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology (Mar 2019) https://www.eurekalert.org/pub_releases/2019-03/cp-vfd022819.php - https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30181-0
Gut microbiota mediates the anti-obesity effect of calorie restriction in mice [Aug 2018] https://www.nature.com/articles/s41598-018-31353-1
Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements (2018, mice): https://doi.org/10.1016/j.cmet.2018.08.005
Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota (2017): http://www.sciencedirect.com/science/article/pii/S1550413117305041 Transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis.
Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota (2018): https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30313-9 Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora.
Food withdrawal alters the gut microbiota and metabolome in mice. food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes in gut microbiota, which were closely associated with the host metabolome. abundance of potentially pathogenic Proteobacteria was decreased and Akkermansia muciniphila was elevated (2018): http://www.fasebj.org/doi/abs/10.1096/fj.201700614R
Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection (Aug 2021, mice) "protection was partially due to the gut microbiome, since fasting was unable to prevent Salmonella infection in mice lacking a microbiome" https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009719
Fasting lowers blood pressure by reshaping the gut microbiota (Feb 2021, rats) Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure https://www.eurekalert.org/pub_releases/2021-04/bcom-flb042921.php
Fasting for 48hrs before chemotherapy drastically & beneficially increased the number & diversity of gut bacteria associated with improved treatment outcomes. Also slowed the turnover of the cells that line the intestines, making them less susceptible to being killed by chemotherapy (Aug 2020, rats) https://medicalxpress.com/news/2020-09-starving-gut-bacteria-chemotherapy-outcomes.html
Caloric restriction disrupts the microbiota and colonization resistance (Jun 2021, mice) "Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota" https://archive.ph/BdQe9#selection-2479.11-2479.12
Other microbiome-related benefits of fasting:
Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology (2019) https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30181-0
Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice (Nov 2018). Previous studies have shown that the gut microbiome is responsible for the benefits of fasting, & the benefits can be transferred via FMT. https://archive.fo/EsoCz#selection-1143.13-1143.14
Detriments of fasting:
Comparative analysis reveals that eating less is beneficial in adult and older primates but is not beneficial for younger animals https://news.wisc.edu/calorie-restriction-lets-monkeys-live-long-and-prosper/ Caloric restriction improves health and survival of rhesus monkeys (2017).
Time-restricted feeding causes irreversible metabolic disorders and gut microbiota shift in pediatric mice (2018): https://www.nature.com/articles/s41390-018-0156-z
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
[Rat study] Nitrogen availability (protein intake) is a main factor in shaping the gut microbiome & health [1]. Low protein, high carb diet associated with beneficial health markers: [1,2]
Low protein diet is recommended based on the evidence that excessive protein intake adversely affect health [1][2][3][4].
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 [1].
There's a big difference between types/sources of fats & proteins [1][2][3]. 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
Prebiotics:
https://humanmicrobiome.info/prebiotics