I first tried low-carbing, circa 2008, and quickly realized just how detrimental it is to health, especially when combined with stress (e.g. “endurance” exercise). At the time, I thought that this dietary fad won’t last long and that mainstream medicine, despite its utter corruption, would eventually rally against the low-carb diets/lifestyle. Fat forward to today, and low-carbing is not only still with us, but it seems to be spreading across the world and is being hailed as one of the greatest breakthroughs in nutrition ever discovered. To be fair, there are some established medical groups that are now actively advising against low-carb diets, including the esteemed medical school at the University of San Francisco, which is one of the top low-carb research centers in the world. However, such contrarian voices remain very rare and they are drowned by a flood of “news” on social media and the blogosphere from famous “influencers” and doctors, who continue to tout the “benefits” of chronic fasting (which mimic low-carb diets physiologically) or low-carb/high-fat/ketogenic diets. Ironically, one of the main reasons given in support of such diets is the fact they increase the production of serotonin (5-HT) in the gut, and since 5-HT is universally accepted as the “happiness hormone”, we are being told that this effect of said diets truly proves that they are indeed “beneficial” for us. Of course, the fact that 5-HT is perhaps the main causal factor of fibrosis (in any organ) is conveniently avoided, or perhaps even medicine has forgotten about 5-HT’s systemic effects, which were well-known as far back as the 1950s. In addition, 5-HT is now known (in some medical circles) to be a cause of depression rather than a cure. I think something worse than incompetence is at play here, since several large pharma companies are quietly running clinical trials with 5-HT antagonists for treating conditions such as lung/heart/kidney disease, and most of the new drugs for depression are at least partially 5-HT receptor antagonists, despite retaining SSRI effects.
Now, if one knows that 5-HT is perhaps the main cause of organ disease/fibrosis and depression, it would be reasonable to expect that anything that promotes 5-HT synthesis in the gut would probably be linked causally to those conditions. Well, since more than 90% of 5-HT is produced in the gut, the main trigger for the bulk of 5-HT production is likely something that activates the enterochromaffin cells in the gut lining, which are the main site of 5-HT synthesis in the gut. That something is, of course, our old friend endotoxin/LPS. It just so happens that the main triggers for endotoxin/LPS elevation (and thus increased 5-HT synthesis) are low-carb/high-fat diets and/or stress (both acute and chronic), with the effects being “synergistic” if both the diet and stress are at play. In other words, given the pathways described so far, one would expect that low-carb/high-fat diets and/or stress to drive both heart disease/fibrosis and mood disorders such as depression, by promoting endotoxin/LPS release and absorption into the bloodstream. Well, that is exactly what the study below demonstrated. In fact, the stress component was not even that severe and is on par with what the vast majority of people living in the Western world experience on daily basis. Namely, the so-called chronic unpredictable mild stress (CUMS), which is widely recognized as the gold standard for causing depression in animal models, yet the role of stress in human mental illness continues to be denied to this day. Well, it looks like the rates of heart disease/failure and depression are not likely to come down any time soon, but would probably continue to rise as millions of people around the world continue to adopt the low-carb/high-fat diets on top of the pervasive CUMS everybody has been subjected to for decades.
https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-025-04302-y
“…A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. ”
“…We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.”
