Increasing knowledge gathered in recent years about the microbes in our gut and their influence in just about every major human disease could lead to a day when you will be taking medications not only for your own health but also to enhance or suppress the actions of microbes in your gut.
Trillions of microbes in our intestine and elsewhere in our body together form the human microbiome. Despite the microbiome outnumbering human cells by 10 to 1, their nanoscopic size means they account for only around one percent of our total body mass. However, the huge impact they have on every aspect of our health is only being realized.
In particular, microbes in our gut that feed on the food we eat make substances called metabolites that can protect or harm our health, with its impact often felt far beyond the borders of our digestive tracts. Previous studies have linked microbial metabolites to a range of chronic diseases, including diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more.
Between 70 to 80 percent of these bacteria come from the phyla Firmicutes and Bacteroidetes, but the mix varies, depending on a person’s genes, environment, and lifestyle. Therefore the combination of what microbes produce differs from person to person, and accordingly, the different biologically active compounds they produce influence people in subtly different ways.
Scientists are now developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites. A new study by researchers at the Center for Microbiome and Human Health at Cleveland Clinic in the United States, suggests that medications for microbes that inhibit the production of specific enzymes they produce, could elicit health benefits against many chronic diseases.
One approach, currently nearing human trials, is a drug that could be taken orally to target the metabolite trimethylamine N-oxide (TMAO), which is a predictor of, and contributor to, both cardiovascular disease and chronic kidney disease. The drug, if it successfully undergoes clinical trials, could prove a boon for patients with heart and kidney conditions. A major advantage of this model is safety, as the drug directly targets only the microbe and is not absorbed into the human body, thereby avoiding secondary complications in patients.
Explaining their finding, researchers behind the new study said that the food we ingest is usually broken down by the gut microbes into metabolites. These metabolites interact with the thin layer of epithelial cells that line our gut, and some of them end up being absorbed through the lining into our bloodstream.
Once in the blood, the metabolites act on the immune cells outside the epithelial lining and influence their functioning, including by triggering irritation and inflammation, potentially leading to a wide variety of health issues, including something as simple as gas formation and stomach bloating to more potent autoimmune conditions, mood disorders, and chronic illnesses.
Of the 1,000-plus metabolites linked to the gut microbiome, scientists have flagged several that influence our health. These include:
Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into beneficial short-chain fatty acids. These bind to receptors in muscle, liver, and fat tissue, affecting gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat burning.
One of these fatty acids, called butyrate, has been linked to health benefits. It strengthens the gut’s lining, stifling bad gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It also functions as a prebiotic, helping beneficial bacteria thrive. More recent studies have linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.
TMAO: When we eat foods rich in animal proteins, especially red meat, some gut bacteria convert nutrients in the meat such as choline and L-carnitine into TMAO. Research done previously has linked this metabolite to heart problems. In a recent landmark study, healthy adults who went on to get coronary artery disease had significantly higher TMAO levels than those who did not wind up with the condition.
Tryptophan: Microbes present in the colon can convert the amino acid tryptophan, found in animal-based foods, into chemical messengers like serotonin and melatonin that impact our mood, appetite and sleep patterns. Other tryptophan metabolites have been linked to benefits like fortifying the gut barrier, promoting the release of the hormone glucagon-like peptide 1 (GLP-1) to reduce appetite, and protecting the liver from hepatitis.
Advances in the field of microbiome research, and the related ‘gut health’ wellness trend have spawned several new microbiome-based products, like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.
But the science behind these tests is still evolving, and the clinical inferences and applications are still pretty limited. For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet. Eat foods and experiment with foods that you might not eat all the time, especially fruits, vegetables, nuts, seeds, and beans.
Another strategy is to eat foods with probiotic bacteria such as yogurt that contain beneficial bacteria. Other fermented foods such as kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics.
Health experts point out that, as with other interventions, individual responses can vary, and that to ensure optimal results from microbiome-based interventions it needs to be personalized. And the technology to do that is coming sooner than you might think, as the new research shows.
AI helps predict brain cell activity using neural maps
For decades, neuroscientists working in laboratories worldwide have spent an immense amount of time and effort to study the activity of neurons (nerve cells) in the brain of live organisms. Their aim was to gain an understanding of how the brain enables behavior in living animals. Research over the years has yielded seminal insights into how the brain functions, but the knowledge garnered in all this time is only a miniscule amount compared to the immense neural activities that take place in the brain and remain explored.
Now, researchers are using artificial intelligence (AI) and the connectome — a comprehensive map of neural connections in the brain — to predict the role of neurons in the living brain. Scientists at the Howard Hughes Medical Institute in the United States, in coordination with researchers at the University of Tübingen in Germany, have developed an AI simulation of the fruit fly visual system that can predict the activity of every neuron in this circuit.
For their study, the scientists used available data on the neural circuit in the common fruit fly’s visual system connectome, and using guesswork on what the neural circuit is supposed to do, they trained the AI to create the simulation. The research resulted in the development of a computational method for turning measurements of the connectome into predictions of neural activity and brain function, without having to first start with the difficult-to-acquire measurements of neural activity of every neuron.
The team used the connectome to build a detailed deep mechanistic network simulation of the fly visual system, where each neuron and synapse in the model corresponds to a real neuron and synapse in the brain. The study provides a new strategy for researchers to bridge the gap between static snapshots of the connectome, and the dynamics of real-life computation in the living brain
Although they did not know the dynamics of every neuron and synapse, data from the connectome allowed the team to use deep learning methods to infer these unknown parameters. They combined this information with knowledge about the circuit’s goal: motion detection.
The new model predicts the neural activity produced by 64 neuron types in the fruit fly visual system in response to visual input and accurately reproduces more than two dozen experimental studies performed over the past two decades.
By enabling researchers to predict the activity of individual neurons using only the connectome, the new work has the potential to transform how neuroscientists generate and test hypotheses about how the brain works. In principle, scientists can now use the model to simulate any experiment and generate detailed predictions that can be tested in the lab.
The new research provides more than 450 pages of predictions gleaned from the new model, including identification of cells not known to be involved in motion detection previously, which can now be examined in living flies.
According to the research team, their findings provide a strategy for turning the wealth of connectome data being generated by other research institutions into advanced understanding of the living brain.
