11 replies to this topic

[MoreGooderFuture]

So, I was wondering...

I've grown interested in probiotics due to all of the hype, and have started taking some store-bought stuff with no noticeable changes in my digestive system.  I'm very open to the concept, but there's just one nagging question:  If friendly bacteria and bad bacteria can both thrive and grow in the gut, then why do we need to take pill after pill of a probiotic? It would seem to me that once you introduce a bacteria strain into the gut it will simply take hold and colonize without further introduction.   Is it because the in the constant gut bacteria battle the good guys don't have a high probability of survival and we must send in reinforcements?  Is it a biological war of attrition? 

[Darryl]

In clinical trials with probiotics, there's little evidence that the introduced bacteria compete effectively for niches with established ones. In those not suffering from infectious or antibiotic related dysbiosis, no effect of probiotics can be found on microbiome consitution, and after probiotic intake is discontinued, introduced strains aren't detected. 

 

Kristensen et al, 2016. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults; a systematic review of randomized controlled trials. Genome medicine, 8(1), p.52.

 

There is little, if any, evidence of an effect of probiotic treatment in circumstances where the microbiota is unperturbed by pathophysiological processes or pharmaceutical treatment (antibiotics or chemotherapy), either concurrent with or prior to intervention. However, where dysbiosis is present or where the microbiota is perturbed, there is some evidence for a restorative or protective effect of certain strains of probiotics, both on the fecal microbial community itself, but more importantly, also on host physiology, e.g. alleviation of gastrointestinal symptoms.

 

This may be because probiotics are made from easily cultured species, which are usually very minor constituents of healthy gut microbiota. The colonic mucosa is a very different environment from a vat of yogurt; the many strains of Lactobaccillus sp. which prodominate in probiotics are not part of the core human microbiome; and earlier studies featuring them are examples of the streetlight effect. The one species I've seen in probiotics that does seem to play an important role is Bifidobacterium longum, seen at 0.3-1.3% in this study: 

 

Martínez et al, 2013. Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species. PloS one, 8(7), p.e69621.

 

Probiotics do shorten the course of post-antibiotic diarrhea, but the past presumption that they were displacing pathogens isn't sound. Perhaps they were competing with pathogens for dietary inputs til resident species recovered, or temporarily filling important links in interdependent metabolic networks, Or, just serving as expensive prebiotic feed for other species. 

 

The consistent message from gut microbiome studies is that the diversity is usually stable from early life, but changes to habitual diet can bring overnight changes to relative composition. If you're not suffering symptomatic disbiosis at the moment, forget about probiotics and seek microbiota accessible carbs, and whole plant phenols.

 

Sonnenburg and Sonnenburg, 2014. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell metabolism, 20(5), pp.779-786.

Mosele et al, 2015. Metabolic and microbial modulation of the large intestine ecosystem by non-absorbed diet phenolic compounds: a review. Molecules, 20(9), pp.17429-17468.

Edited by Darryl, 18 November 2017 - 03:08 PM.

[sthira]

The consistent message from gut microbiome studies is that the diversity is usually stable from early life, but changes to habitual diet can bring overnight changes to relative composition. If you're not suffering symptomatic disbiosis at the moment, forget about probiotics and seek microbiota accessible carbs, and whole plant phenols.

Sonnenburg and Sonnenburg, 2014. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell metabolism, 20(5), pp.779-786.
Mosele et al, 2015. Metabolic and microbial modulation of the large intestine ecosystem by non-absorbed diet phenolic compounds: a review. Molecules, 20(9), pp.17429-17468.

Good advice as usual, Darryl: for happier guts, whole plants, lots of greens, veggies high in prebiotic fermentable fiber. Some biggie prebiotics are raw jicama (yum), dandelion greens (delicious), raw Jerusalem artichokes (crunchy, earthy, oddly addictive), leeks, onions, garlic, asparagus, raw wheat bran...

For probiotics, no to expensive pills, drink some kefir instead, eat some kimchi, a bit of harsh sauerkraut, cool your sweet potatoes off after steaming them to goodness.

Eat plants, humanoids: your body's your temple, you have nowhere else to live but within it, these limbs are attached to this spine, so feed it kindly, work the body out hard then work it easy, and stay mindful, find trees, they help your gut, climb into the dirty canopy like an ape, get filthy, and keep the chin up despite the loud human world that's screeching endlessly about money and money and money and how it's all is falling to shit. Also kiwi fruit feeds your mucin, so eat the skins.

[normalizing]

thats a good question actually. the thing is, its business. you have to take one two three... thousand caps cuz they cost money and there is the theory thats how you introduce the bacteria to your body by being "persistent" in spending the money.

anyway, just eat fermented foods, they have been the probiotic of ancient times and you only spend the money to feed yourself, not swallow pills

[Dorian Grey]

I don't have a lot of links to research on this, but from what I understand pre & probiotics help tip the ratio of gram positive (good bugs) to gram negative (bad bugs) in the stool itself as it passes through the colon.  

 

When the ratio of gram negative bacteria is high, there is a lot of "endotoxin" present in the stool, and as water is drawn out of feces in the colon, something called "Lipid-A" can carry this endotoxin through the gut wall into portal circulation, which causes an immune response, primarily in the liver.  

 

https://en.wikipedia.org/wiki/Lipid_A

 

When the ratio of gram negative bacteria is reduced, through pre & probiotic therapy, there is less endotoxin in the stool, and therefore less immune related inflammation from endotoxin absorbed through the colon.  

 

Lactobacillus is supposed to be particularly helpful, as the lactic acid it secretes is supposed to suppress growth of gram negative bacteria.  

 

https://www.ncbi.nlm...cles/PMC101446/

 

"Roth and Keenan reported in 1971 (26) that lactic acid is able to cause sublethal injury to Escherichia coli, and similar properties have also been assigned to acetic acid (23); indirect evidence inferred that such injury involved disruption of the LPS layer. A permeabilizer function of lactic acid would not only be utilizable in decontamination procedures and in protective cultures but it would also provide a mechanistic explanation supporting the antimicrobial and health-promoting effects of probiotic lactic acid bacteria"

 

Probiotics may not permanently colonize in the colon wall, but anything that suppresses growth of gram negative bacteria, even in the stool itself as it passes through the colon should reduce the load of endotoxin in portal circulation and inflammation in the liver.  

 

Entotoxin is such a potent promoter of inflammation and immune response, it has been proposed as the basis of systemic disease initiated from the limited generation of endotoxin in periodontal disease.  If the small amounts of endotoxin from gum disease can affect health, imagine what the load of endotoxin from half a kilo of stool mass might create.

 

https://www.ncbi.nlm...icles/PMC88948/

 

Sorry I don't have the time to dig up more references, but if you do your own homework you should find this is the basis of pre & probiotic therapy.  

 

One weakness of probiotics is whether they actually survive stomach acid to thrive in stool. Lactobacillus rhamnosus found in "Culturelle" brand has been found to pass the acid test, and this is what I've used with good results.  

 

Prebiotics (FOS & inulin) don't have this problem and support bifidobacterium and I take these too!  

Edited by Dorian Grey, 21 November 2017 - 05:37 AM.

[Darryl]

Remember, stool is more than half bacterial cells, by weight or volume. There's still an ample amount of gram negative bacteria to provide endotoxins for systemic inflammation, regardless of diet or probiotic intake.

 

I've studied metabolic endotoxemia intently over the past few years, and agree that it probably mediates many adverse effects of high-fat, high-added-sugar, and high alcohol diets in inflammatory chronic diseases, which were hitherto attributed to their physiology once absorbed.. In the course of this, I intently looked at every intervention I could find that has reduced circulating endotoxins. Prebiotics, dietary polyphenols, low-fat diet, low-sugar diet, and adequate intake of zinc and vitamin C all appear to help. While probiotics have mixed results in effecting intestinal barrier function as measured by laculose/mannitol and similar tests, I've yet to encounter a study where a currently commercial prebiotic improved serum endotoxin levels. The story for current prebiotics in chronic disease isn't encouraging. 

 

Prebiotics / fermentable fiber / microbiota available carbs / FODMAPS

Keshavarzian et al, 2001. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. Journal of Pharmacology and Experimental Therapeutics, 299(2), pp.442-448.

Cani et al, 2009. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 58(8), pp.1091-1103.

Xiao et al, 2014. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome. FEMS microbiology ecology, 87(2), pp.357-367.

Leelasinjaroen et al, 2014. Su1487 Bifobacteria infantis contributes significantly to the beneficial effects of oligofructose (prebiotic) to prevent mucosal inflammation, metabolic endotoxemia and hyperphagia induced by high fat feeding. Gastroenterology, 146(5), pp.S-482.

Dehghan et al, 2014. Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized-controlled clinical trial. International journal of food sciences and nutrition, 65(1), pp.117-123.

 

Polyphenols and other phytochemicals

Ghanim et al, 2010. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. The American journal of clinical nutrition, 91(4), pp.940-949.

Ghanim et al, 2011. A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. The Journal of Clinical Endocrinology & Metabolism, 96(5), pp.1409-1414.

Goodrich et al, 2012. Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats. Nutrition research, 32(10), pp.787-794.

Peng et al, 2013. Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression. Journal of Pharmacology and Experimental Therapeutics, 344(3), pp.646-654.

Everard et al, 2012. Tetrahydro iso-alpha acids from hops improve glucose homeostasis and reduce body weight gain and metabolic endotoxemia in high-fat diet-fed mice. PloS one, 7(3), p.e33858.

Gu et al, 2014. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice. The Journal of nutritional biochemistry, 25(4), pp.439-445.

Camargo et al, 2014. Olive oil phenolic compounds decrease the postprandial inflammatory response by reducing postprandial plasma lipopolysaccharide levels. Food chemistry, 162, pp.161-171.

Roquetto et al, 2015. Green propolis modulates gut microbiota, reduces endotoxemia and expression of TLR4 pathway in mice fed a high-fat diet. Food Research International, 76, pp.796-803.

Masumoto et al, 2016. Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes. Scientific reports, 6, p.31208.

 

Low-fat diet (limited to human studies, or else I'll be here all night)

Erridge et al, 2007. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. The American journal of clinical nutrition, 86(5), pp.1286-1292.

Amar et al, 2008. Energy intake is associated with endotoxemia in apparently healthy men. The American journal of clinical nutrition, 87(5), pp.1219-1223.

Ghanim et al, 2009. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal. Diabetes care, 32(12), pp.2281-2287.

Deopurkar et al, 2010. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes care, 33(5), pp.991-997.

Pendyala et al, 2012. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology, 142(5), pp.1100-1101.

Harte et al, 2012. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes care, 35(2), pp.375-382.

Clemente-Postigo et al, 2012. Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients. Journal of lipid research, 53(5), pp.973-978.

Zaman et al, 2014. Comparison of postprandial endotoxemia in male adolescents and male subjects above 50 years after a fat overload. Int J Curr Res Acad Rev, 2, pp.167-174

Lyte et al, 2016. Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study. Lipids in health and disease, 15(1), p.186.

Vors et al, 2017. Emulsifying dietary fat modulates postprandial endotoxemia associated with chylomicronemia in obese men: a pilot randomized crossover study. Lipids in health and disease, 16(1), p.97.

 

Low added-sugar diet (limited to hominoid studies)

Thuy et al, 2008. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. The Journal of nutrition, 138(8), pp.1452-1455.

Kavanagh et al,,2013. Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. The American journal of clinical nutrition, 98(2), pp.349-357.

Jin et al, 2014. Fructose induced endotoxemia in pediatric nonalcoholic fatty liver disease. International journal of hepatology, 2014.

 

Adequate zinc

Lambert et al, 2003. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. Journal of Pharmacology and Experimental Therapeutics, 305(3), pp.880-886.

 

Adequate vitamin C

Tokuda et al, 2015. Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats. Nutrition, 31(2), pp.373-379.

 

Failed attempts with currently probiotics

Leber et al, 2012. The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study. European journal of clinical nutrition, 66(10), pp.1110-1115.

Lee et al, 2014. The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: a randomized double-blind controlled clinical trial. Clinical Nutrition, 33(6), pp.973-981.

 

Positive result for Akkermansia.

Li, et al, 2016. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-/-mice. Circulation, pp.CIRCULATIONAHA-115.

 

I am enthused about results with Akkermansia, which may someday become available as a prescription probiotic, or cultured for its membrane proteins which have a similar effect in inducing mucin production. I probably have written about it elsewhere, but the interventions that increase Akkermansia parallel those that reduce endotoxemia: inulin and other oligofructans (Allium vegetables like onions, leeks, garlic), alpha-galactosides (beans), arabinoxylan (wheat/rye/barley bran, or their whole grains), fucoidan (seaweed), resistant starch (pasta, retrograded starches, high amylose corn), polyphenols (ubiquitous in fruit, esp dark colored berries), capsaicin (hot peppers). On the other hand, high protein diets reduce Akkermansia levels. I can add sources for Akkermansia changing interventions sources here later, if there's interest.

 

 

Edited by Darryl, 21 November 2017 - 07:37 PM.

[normalizing]

darryl, what do you mean by high fat diet? salmon, avocados, olive oil, coconut oil, are all high fat diets, so they raise endotoxin levels and should be avoided? im curious from perspective of ketogenic diet which is shown to actually decrease inflammation and ketogenic diet doesnt nessesary uses the healthy fats either

[pamojja]

darryl, what do you mean by high fat diet? salmon, avocados, olive oil, coconut oil, are all high fat diets, so they raise endotoxin levels and should be avoided? im curious from perspective of ketogenic diet which is shown to actually decrease inflammation and ketogenic diet doesnt nessesary uses the healthy fats either

 

Usually these high fat diets trials aren't low-carb or even keto, but with SAD amounts of carbs. And that combination for sure is deathly.

Edited by pamojja, 21 November 2017 - 08:38 PM.

[sthira]

I can add sources for Akkermansia changing interventions sources here later, if there's interest.

Yes there's interest! Your posts are fantastic, and when you share your research we all benefit. That's why we love you, and encourage you to keep writing!

[Dorian Grey]

I've always had great respect for Darryl too, and it looks like he's bested me here.  

 

Magnificent brain there mate.  Keep sharing your knowledge!  

[Darryl]

Hazy: A wide variety of fats have induced postprandial endotoxemia in humans and lab animals. Coconut oil, palm oil, lard, butter, whipping cream, soybean oil, corn oil, sunflower oil, sunflower oil emulsion, triolein, margarine, sausage muffin and hash browns, Western-style diet. When the effects of different fats are compared, saturated fats tend to increase endotoxin load more then n-3 polyunsaturated fats, and emulsified fats (think creamy dressings, mayo, ice cream) cause larger spikes than the same fat in its native state. The endotoxins are  packaged with absorbed fats in chylomicrons to enter systemic circulation. 

Edited by Darryl, 22 November 2017 - 12:50 AM.

[Darryl]

Those Akkermansia papers:

 

Van den Abbeele et al, 2011. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin‐degradation in humanized rats. Environmental microbiology, 13(10), pp.2667-2680.

Everard et al, 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences, 110(22), pp.9066-9071.

Sybille et al, 2013. The intestinal microbiota in aged mice is modulated by dietary resistant starch and correlated with improvements in host responses. FEMS microbiology ecology, 83(2), pp.299-309.

Anhê et al. 2015. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut, 64(6), 872-883.

Roopchand et al, 2015. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet–induced metabolic syndrome. Diabetes, 64(8), pp.2847-2858.

Monk et al, 2016. Navy bean supplementation in obesity increases Akkermansia muciniphila abundance and attenuates obesity related impairments in gut barrier function. The FASEB Journal, 30(1 Supplement), pp.421-2.

Mu et al, 2016. The colonic microbiome and epithelial transcriptome are altered in rats fed a high-protein diet compared with a normal-protein diet. The Journal of nutrition, 146(3), pp.474-483.

Holmes et al, 2016. Diet-microbiome interactions in health are controlled by intestinal nitrogen source constraints. Cell metabolism, http://dx.doi.org/10...met.2016.10.021

Shang et al, 2017. Dietary fucoidan improves metabolic syndrome in association with increased Akkermansia population in the gut microbiota of high-fat diet-fed mice. Journal of Functional Foods, 28, pp.138-146.

Henning et al, 2017. Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo. Anaerobe, 43, pp.56-60.

Shen et al, 2017. Anti-obesity effect of capsaicin in mice fed with high-fat diet is associated with an increase in population of the gut bacterium Akkermansia muciniphila. Frontiers in microbiology, 8.

Catry et al, 2017. Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction. Gut, pp.gutjnl-2016.

Edited by Darryl, 22 November 2017 - 05:00 AM.