July 01, 2026
Inflammation, Residual Risk, & Our Largest Immune Organ
Analogies go a long way in educating about unfamiliar topics. Let’s start with two.
1) Our collective understanding of the gut microbiome and the countless strands connecting it to different aspects of overall health mirrors our understanding of the genome, or DNA, before Y2K. Back then, we knew what DNA was, how it was structured, and a few key details. Beyond that, we were grasping at straws. Sequencing one person’s genome took tens of thousands of dollars and a lot of time. In 2025, that cost is pennies on the dollar, results are near instant, and the average person can access tailored information about their DNA (think 23andMe).
With understanding came therapies, and now CRISPR can change DNA to cure sickle cell disease, with FDA approval for this coming in 2023. For perspective, Watson and Crick identified DNA’s structure back in 1953. It only took one lifetime, or 70 years, for understanding to translate into action. Thankfully, science moves much quicker these days.
2) The gut microbiome is essentially the body’s operating system (OS). It’s the “second brain” running processes in the background, and the signals to our organs are just 0s and 1s, binary code dictating how the software should process inputs for specific outputs. This framework makes a lot of sense when you consider just how deeply intertwined the makeup and “health” of the gut microbiome are with the brain, the heart, even how people with the same subset of cancer respond to the same immunotherapy.
So, what is the gut microbiome?
Simply put, it’s the microscopic inhabitants of our gut. It’s trillions of tiny “microorganisms,” mostly bacteria, that live alongside us. If you look at the DNA contribution, they contribute ~3 million unique genes, compared with the 20,000 genes in a human genome, outnumbering us by a factor of 150. That first analogy is already paying off, isn’t it?
Microbial cells outnumber human cells, and each person carries their own unique “fingerprint” of hundreds of species, making tailored therapies a very real possibility in the not too distant future. Our microbes process carbohydrates, breaking down fiber human guts can’t process, forming energy sources through short-chain fatty acids (SCFAs) for the cells lining our small intestine. They make vitamins and micronutrients we can’t make on our own. They break down protein for us, and they do the same for bile acids which then help the liver “digest” fat. This affects our metabolism, sometimes for better and sometimes for worse.
The kicker is how they factor into our immune system. The gut is the single largest immune organ in the body, housing ~70-80% of our immune cells, and our microbes are the architects dictating what our immune regulation looks like throughout our lives. Bad microbes foster inflammation, driving heart disease, certain types of dementia, and even cancer. Our microbes “educate” our immune system as soon as we’re born, and that education, just like our own education, can look very different for different people. A bad education can plague you for life, and similarly, immune cells without the proper “schooling” recognize normal things as abnormal, leading to allergies and autoimmune disease.
Over 90% of our body’s serotonin is produced in the gut. Key players in that production, along with production of dopamine and GABA (the molecule anti-anxiety medications mimic to treat psychiatric issues like depression and anxiety), are microbes. Microbes are so tightly linked to communication between the gut and brain that the gut is often called our “second brain.” Talk about a “gut feeling.”
Okay, all of that is great, but what determines a “healthy” gut microbiome?
Think of a rainforest. Pick anywhere in the forest, and you’ll run out of fingers and toes well before you can count the different species just in eyesight. The gut microbiome is no different. Diversity is good here. Different species perform different tasks, and just like with farming, relying on a single crop eventually takes its toll. You need more than just corn in your diet, and your gut needs more than X bacteria to thrive.
Diversity leads to resilience. Infections happen, and antibiotics are a necessary evil. Without them, we’d still be dropping dead from Montezuma’s revenge, but they can ravage the gut microbiome. Having different species helps protect against catastrophe. In fact, catastrophe of this sort is what helped promote the study of the gut microbiome. Clostridium difficile, better known as C. diff, grows when there’s opportunity. When antibiotics kill off healthy and helpful bacteria, C. diff can now use your body’s resources to grow, multiply, and cause infection.
Before we knew about bacteria, “yellow soup” was being used in 4th century China to treat diarrhea. “Yellow soup,” it turns out, was a poop slurry, and it worked. In 1958, the first “fecal microbiota transplant” (FMT) was used to cure colitis. The researchers had a hunch that antibiotics killed off helpful bacteria and thought reintroducing bacteria through the poop of healthy folks would help counter the problem. The concept understandably met resistance, so it wasn’t until a landmark trial in 2013 proving FMT cured repeat C diff infections that the concept became mainstream. A side effect was interest in what kinds of microbes our gut is home to, and that’s how the NIH’s Human Microbiome Project came about.
Great! Now, what’s an unhealthy gut microbiome?
Growth of “bad” bacteria is called “dysbiosis.” The term signifies an imbalance, a tipping point where our microbes are working against us more than with us. The types of microbes can be infection-causing, or they can be silent while upping inflammation throughout our bodies. Dysbiosis is tightly linked to “modern” diseases, and much of this comes from the modern diet of industrialized parts of the world, where fast food is king and everything we eat is processed. IBD, IBS, obesity, heart disease, fatty liver disease, allergies, eczema, psoriasis, depression, anxiety, and more can all be traced to contributions from bad microbes treating us badly.
Again, the targets are endless, and just like with DNA, understanding builds to critical mass until therapies follow. The gut microbiome is a new frontier, and we learn more every day. The more we understand, as normal people, the more we can make changes that keep our microbes working for us rather than against us. There’s more to come, and by the end, we’ll know enough to be able to optimize our chances at healthy living.
Stop by more often if you learned something. If you want to learn more, read some shorter pieces on our blog or even shorter pieces through our newsletter. Pop your email address in our newsletter, sign up for ultra-bite sized education, for regular bite-sized education. Dr. Bilal Ahmed MD MBA & Zoya Ahmed are great resources too.
