Prebiotics - Overview, Risks & Harms, Benefits
A substrate that is selectively utilized by host microorganisms conferring a health benefit.
"There is much less evidence on the efficacy and safety of prebiotics than probiotics" (Sept 2019)
Review, Nov 2019: The effects of inulin on gut microbial composition: a systematic review of evidence from human studies https://link.springer.com/article/10.1007%2Fs10096-019-03721-w "The most consistent change was an increase in Bifidobacterium. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels"
Review: Oligosaccharides: a boon from nature’s desk 
Review: Food Additives and Contaminants (including antibiotics): Effects on Human Gut Microbiota 
Review: Impact of Dietary Fibers on Nutrient Management and Detoxification Organs: Gut, Liver, and Kidneys 
Review: The Critical Roles of Polysaccharides in Gut Microbial Ecology and Physiology 
Review: Meeting the diverse requirements of gut microbes through diverse prebiotic compounds. Isomalto-oligosaccharides, Fructooligosaccharides, Xylooligosaccharides, Galactooligosaccharides, Polyphenols, Pectin, Resistant starch, Guar fiber, Acacia, Aloe. 
Chart showing effects of prebiotics from multiple studies (IE: bifidogenic), (2018): https://link.springer.com/article/10.1007%2Fs12325-018-0673-5#Sec4
Prebiotics (resistant starches specifically) must be accompanied by a high carb diet in order to reap the benefits, and can have detrimental impacts when accompanied by a low carb diet: https://archive.fo/v5FwS
In the absence of microbes, inulin and short-chain fructo-oligosaccharide (scFOS) directly promote barrier integrity to prevent pathogen-induced barrier disruptions. So prebiotic benefits extend beyond their impact on microbes: http://www.nature.com/articles/srep40820
Non-digestible oligosaccharides directly regulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0357-4
Polish wild mushroom polysaccharides stimulate the growth of Lactobacillus strains stronger than commercially available prebiotics like inulin or FOS: https://link.springer.com/article/10.1007%2Fs00394-017-1436-9
Fiber Supplements Derived From Sugarcane Stem, Wheat Dextrin and Psyllium Husk Have Different In Vitro Effects on the Human Gut Microbiota (2018): https://www.frontiersin.org/articles/10.3389/fmicb.2018.01618/full
"A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host."
Taking probiotics in the same meal as prebiotics can change the impact of the prebiotic.
Review, Nov 2019: Resistant starch: impact on the gut microbiome and health https://www.sciencedirect.com/science/article/pii/S0958166919301077 "Microbiome composition is a key determinant of resistant starch outcome. Personalization, matching resistant starch to a microbiome may be needed."
Review, Jun 2017: Resistant Starch Regulates Gut Microbiota: Structure, Biochemistry and Cell Signalling
Video visualizing how resistant starch & butyrate beneficially impact the gut and health: https://www.youtube.com/watch?v=NI3KtR3LoqM
Article on resistant starch with comparison chart: https://www.precisionnutrition.com/all-about-resistant-starch
General article on resistant starches: http://www.theglobeandmail.com/life/health-and-fitness/health/boost-your-intake-of-resistant-starch-to-help-your-gut-thrive/article33618103
Review, Aug 2020: Short chain fatty acids in human gut and metabolic health https://www.wageningenacademic.com/doi/10.3920/BM2020.0057
The role of short-chain fatty acids (SCFAs) - a group of molecules that result from fermentation of dietary fibers by the gut microbiota. https://fityourself.club/the-role-of-short-chain-fatty-acids-41fa3f14409f
SCFAs are thought to play a key role in increasing the host capacity to harvest excess energy from the diet. SCFAs, however, can exert their effects on the host metabolism via multiple complementary pathways. Metabolic, inflammatory, and neural pathways can be regulated by SCFAs, which can act by sensing nutritional status, thereby maintaining body energy homeostasis (Mar 2019): https://link.springer.com/article/10.1007/s42000-019-00100-0
FOS vs Inulin:
FOS is a type of inulin. FOS may feed harmful bacteria more than inulin. Plus additional discussion and source for pure inulin: https://archive.fo/kr88w
Whole foods > processed:
Purified soluble fibers cannot replace natural fiber rich diet (in regards to protecting mucus barrier)[1,2,3]. And supplementing a low fiber/carb diet with prebiotics can actually have detrimental effects.
Whole grains > brans & refined grains .
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 .
Prebiotics found in whole foods such as seaweed^, mushrooms^, and garlic & bananas , can be as, or more, powerful than refined versions like Inulin & FOS.
Anecdotally, in myself, I have no problems with foods high in prebiotics, but purified versions like Inulin/FOS supplements, and blends like this one (oligo30) trigger a variety of detrimental effects for me. Though Bimuno (GOS) is mostly only beneficial for me.
Significant variation from person to person:
"results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement" (Jan 2019, n=174). Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers: https://mbio.asm.org/content/10/1/e02566-18
The same diet has very different effects on each microbiota’s membership and function, which may in turn explain interindividual differences in response to a dietary ingredient http://msystems.asm.org/content/1/5/e00098-16
Responses to dietary supplementation with resistant starch (unmodified potato starch) varies wildly https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0178-x
Healthy subjects differentially respond to dietary capsaicin correlating with the specific gut enterotypes http://press.endocrine.org/doi/10.1210/jc.2016-2786
Variation depending on age .
Variation on impact of polyphenol supplementation in men vs women https://www.nature.com/ejcn/journal/vaop/ncurrent/full/ejcn201789a.html
Inter-individual differences determine the outcome of wheat bran colonization by the human gut microbiome http://onlinelibrary.wiley.com/doi/10.1111/1462-2920.13819/full
BBC Two: firm links between a person’s individual response to food, and to the gut bacteria that they have.
Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids: https://www.nature.com/mi/journal/vaop/ncurrent/full/mi201775a.html
Cravings for high-calorie foods may be switched off by inulin http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_1-7-2016-10-31-12
Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201600716/abstract
Prevent the Development of Hypertension and Heart Failure in DOCA-Salt Hypertensive Mice.
Prevent intestinal dysbiosis and obesity-associated metabolic disorders in obese individuals http://www.sciencedirect.com/science/article/pii/S2352396417300233
scFOS significantly reduced anxiety scores, increased fecal Bifidobacteria, and improved IBS http://onlinelibrary.wiley.com/doi/10.1111/nmo.12911/full
GOS helps with lactose intolerance.
Resistant starches improve insulin sensitivity http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0230-5
Butyrate restores HFD induced adaptations in brain function and metabolism in mid-adult obese mice http://www.nature.com/ijo/journal/vaop/naam/abs/ijo201752a.html#aff1
The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain https://www.ncbi.nlm.nih.gov/pubmed/19549282
Inonotus obliquus [mushroom] polysaccharide (IOP) regulates gut microbiota composition and diversity to a healthy profile in mice with chronic pancreatitis. http://amb-express.springeropen.com/articles/10.1186/s13568-017-0341-1
Dietary Prebiotics (lactoferrin & milk fat globule membrane) and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity http://journal.frontiersin.org/article/10.3389/fnbeh.2016.00240/full
Prebiotics (FOS+GOS) Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice http://www.sciencedirect.com/science/article/pii/S0006322317300422
Inulin-type fructans improve endothelial dysfunction http://gut.bmj.com/content/early/2017/04/04/gutjnl-2016-313316
Review, 2018: Harms Reporting in Probiotics, Prebiotics, and Synbiotics Trials "Harms reporting is often lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data." http://annals.org/aim/article-abstract/2687953/harms-reporting-randomized-controlled-trials-interventions-aimed-modifying-microbiota-systematic
UToledo research finds link between refined dietary fiber, gut bacteria and liver cancer. The new study challenges conventional wisdom that dietary fiber is good no matter how you get it. While the inulin-containing diet did stave off obesity in 40 percent of mice, many of those same mice went on to develop liver cancer at the end of the six-month study. (2018): https://www.eurekalert.org/pub_releases/2018-10/uot-urf101718.php - "Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer"
Stopping or reducing dietary fiber intake reduces constipation and its associated symptoms (2012): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435786/
Overall, inulin did not reduce hypercholesterolemia or atherosclerosis development in E3L.CETP mice despite showing clear prebiotic activity, but resulted in manifestations of hepatic inflammation when combined with a high percentage of dietary cholesterol (2018) https://www.nature.com/articles/s41598-018-34970-y The prebiotic inulin modulates gut microbiota but does not ameliorate atherosclerosis in hypercholesterolemic APOE*3-Leiden.CETP mice
Low FODMAP diet is a popular diet that avoids prebiotic substances, since they are known to be detrimental for people with various types of gut dysbiosis: https://gut.bmj.com/content/66/8/1517 - https://www.ncbi.nlm.nih.gov/pubmed?term=FODMAP%5BTitle%5D
Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity (2017, n=59): https://www.gastrojournal.org/article/S0016-5085(17)36302-3/fulltext
FODMAPs, but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial (Oct 2021, n=110) https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab337/6382986
"Exacerbation of IBS symptoms after wheat and barley consumption is due to their fructan, and not related to their gluten content in most of the patients" (Dec 2021, n=49) https://clinicalnutritionespen.com/article/S2405-4577(21)01166-9/fulltext The Effect of Low FODMAP Diet with and without Gluten on Irritable Bowel Syndrome: A Double Blind, Placebo Controlled Randomized Clinical Trial.
Adult celiac disease with persistent IBS-type symptoms: a pilot study of an adjuvant FODMAP diet (2021, n=25) https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8514221/ "first study to demonstrate that an adjunct LFD is an effective dietary treatment for concurrent IBS in adult CD patients with biopsy-confirmed remission"
"A low FODMAP diet can improve pain intensity and QoL among children with functional abdominal pain" (Nov 2022, n=50) https://pghn.org/DOIx.php?id=10.5223/pghn.2022.25.6.510 Effects of a Low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyol Diet on Symptoms of Functional Abdominal Pain in Pediatric Patients
Unfermented β-fructan fibers fuel inflammation in select inflammatory bowel disease patients (Sep 2022) https://www.gastrojournal.org/article/S0016-5085(22)01150-7/fulltext
Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation (2017): https://academic.oup.com/ibdjournal/article/24/1/101/4757510
Sialic acid (acidic oligosaccharides) may contribute to cancer formation: https://archive.is/Ag7r7
Both FOS & inulin can feed opportunistic microbes & worsen SIBO symptoms for some people: http://fixyourgut.com/dont-recommend-use-foss-improving-gut-health/
The metabolism of butyrate, known to reduce plasma glucose levels, was significantly downregulated in the GOS-fed mice, an effect potentially detrimental to the glucose metabolism of the host (2018): http://pubs.rsc.org/en/content/articlelanding/2018/fo/c7fo01720k#!divAbstract
Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population (2017): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603605/
In an infectious condition, SCFAs may exert a detrimental effect on the host by inhibiting neutrophil's effector functions: http://onlinelibrary.wiley.com/doi/10.1111/cmi.12720/abstract
The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans (April 2019): https://stm.sciencemag.org/content/11/489/eaav0120
Acetate mediates a microbiome-brain-β cell axis promoting metabolic syndrome: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922538/
Increase in serum SCFAs was associated with increased tuberculosis susceptibility in HIV patients on antiretroviral therapy (Mar 2017): https://doi.org/10.1016/j.chom.2017.03.003
"high blood levels of certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain" (2020) https://medicalxpress.com/news/2020-11-link-alzheimer-disease-gut-microbiota.html