The virtual flood of science pouring out informing us that the gastrointestinal (GI) microbiome plays a critical role in virtually all modern diseases should cause us to question many of the findings that have become accepted as gospel, studies in which the contribution of the GI microbiome has not been addressed. In other words, in many studies, the role of the GI microbiome has not been factored in, potentially causing false conclusions to be reached.

Consider these examples:

  • Eating fish, chicken, beef and other carnitine- and choline-containing foods increases blood levels of trimethylamine oxide, TMAO. Conclusion: eating fish, chicken, beef and other animal products causes heart disease. This conclusion, however, ignores the fact that TMAO production depends on the composition of bowel flora. If bowel flora is disrupted, as it is in a large proportion of Americans, with abnormal increases, for instance, in species of Bacteroidetes and Proteobacteria, TMAO production is increased. The problem is therefore not the foods that have been part of the human dietary experience for millions of years and for which the human body is adapted; the problem is bowel flora processing. Reporting that fish, chicken, beef, etc. are causes of heart disease is naively premature and likely not true.
  • Higher levels of homocysteine, especially 14 mcmol/L or greater, have been conclusively associated with several-fold greater risk for cardiovascular disease, depression, and cancers. Eight randomized, placebo-controlled clinical trials have been conducted in which various regimens of vitamins B6, B9 (folate or folic acid), B12, and sometimes B2 have been compared to placebo: no reduction in adverse outcomes. In other words, there is a disconnect between increased homocysteine and B vitamin status. Many species of bowel flora that have been reduced or lost by modern lifestyles, including L. reuteri, are producers of B vitamins. You can see the flawed logic here: increased homocysteine is likely not due to a lack of B vitamins per se, but is due to disruption of the GI microbiome species that produce B vitamins that is not corrected by supplementing B vitamins. The solution would therefore be to directly address the GI microbiome.
  • Time-restricted eating (TRE) and intermittent fasting (IF) yield improvements in insulin resistance, blood sugar, blood pressure, inflammatory markers, and can facilitate weight loss. A number of explanations have been offered to account for these effects, including augmentation of autophagy. But consider: By my estimation, half the U.S. population has small intestinal bacterial overgrowth, SIBO, as evidenced across the numerous studies asking the question: What proportion of people with  _____ (fill in health condition) test positive for SIBO by breath hydrogen (H2) gas measurement? For example, of the 110 million Americans who are obese, what proportion test positive for SIBO? 50%. That means that 55 million people who fall into this category alone have SIBO. How about irritable bowel syndrome (IBS)? Of the 60-70 million Americans with IBS, approximately 40% test positive for SIBO, or another 24+ million people. Add up the number of people with fatty liver, type 2 diabetes, fibromyalgia, autoimmune conditions, neurodegenerative conditions, sleep apnea, restless leg syndrome, etc., who test positive for SIBO and you can appreciate that the number of people with SIBO is staggering, easily exceeding 100 million. SIBO is accompanied by endotoxemia that drives insulin resistance, inflammation, higher blood sugar, higher C-reactive protein, and makes weight loss difficult or impossible. Studies that assess the effects of TRE and IF did not screen people for SIBO or endotoxemia. Are the benefits of TRE and IF really just due to a reduction in bacterial species in the GI tract and thereby endotoxemia due to reduced intake of prebiotic fibers and other microbiota-accessible carbohydrates metabolizable by bowel flora? My bet is that the benefits of TRE and IF are really due to these bowel flora effects. The real solution is therefore not changing eating patterns, but addressing bowel flora. If you only address eating patterns, you do not correct the underlying GI dysbiosis that leaves you at long-term risk for conditions such as ulcerative colitis, diverticular disease, and colon cancer. It is therefore wise to address bowel flora and not confine efforts to changes in dietary schedules. This does not mean that TRE or IF are harmful; it means that you may, by following such eating schedules, be failing to address a very important aspect of health that can, over a longer period, lead to development of common diseases.
  • Ketogenic and carnivorous diets have grown in popularity due to the profound upfront effects in losing weight, reducing blood sugar and blood pressure, reversing fatty liver and high triglycerides, and reducing symptoms of IBS. There is no question that extremes of carbohydrate-avoidance yield near-term metabolic benefits. The problem comes, however, when you deprive the GI microbiome of microbiota-accessible carbohydrates (MACs), AKA prebiotic fibers, resistant starches, polysaccharides, etc., as well as polyphenols. Numerous GI microbial species are reduced or die-off due to “starvation,” much as a dog tied up in the backyard and not fed will be dead within a week. The peculiar phenomenon that emerges, however, in the GI microbiome is that there are species that thrive by resorting to consumption of human intestinal mucus, species such as Akkermansia muciniphila (mucin + phial = mucus lover) that, under ordinary circumstances are beneficial. But when deprived of MACs, Akkermansia populations expand to 18%, 24%, 36% or more of the entire GI microbiome and thins or destroys the intestinal mucus barrier. This leads to intestinal inflammation, conditions such as ulcerative colitis, diverticular disease, and increased risk for colon cancer, while also increasing endotoxemia, i.e., the entry of microbial breakdown products into the bloodstream. MAC deprivation also leads to over proliferation of cancer-causing hydrogen sulfide-producing species such as Desulfovibrio. Long-term, these lifestyles therefore reverse all the upfront benefits with weight regain, higher blood sugar and blood pressure, higher triglycerides, disruptions of GI health. This is not my speculation, but observations borne out over the last 100 years in children who followed ultra-low carb diets to help subdue intractable grand mal seizures.

Over and over again, presumed cause-effect relationships have been reached only to fall apart in light of the contribution of the GI microbiome. We should therefore stop jumping to conclusions without first factoring in the contribution of the GI microbiome. If all this talk about the GI microbiome is foreign to you or you’re having a hard time understanding it, I would urge you to start with my Super Gut book that walks you through such issues, including practical strategies to deal with all the above issues. I also conduct in-depth discussions about the GI microbiome in my website, including in the membership Inner Circle. Just this past Wednesday, for instance, we spent 2 hours discussing various topics relevant to the GI microbiome via live two-way Zoom.