Sometimes, I wish I could disappear into the soufflé-like gloom of PG Wodehouse instead of reading about the leading causes of cancer death in people under 50.
The good news is that a new study from the American Cancer Society found that the overall cancer death rate among people under 50 has declined; Except for one type of cancer, colorectal, which is now the cancer with the highest mortality rate in that group.
I told myself, maybe this damage has to do with the American diet and lifestyle. But my uneasiness vanished when I turned to India’s data and found that, here too, the incidence of colorectal cancer is rising rapidly, with 64,863 cases and 38,367 deaths in 2022. The North-East and cities like Delhi, Bengaluru and Thiruvananthapuram appear as hotspots.
What is happening? Why are relatively young people dying from this disease of the “old people”?
The list of co-morbidities – obesity, diabetes, inflammatory bowel disease (IBD; which is skyrocketing in India) – is suggestive, as is the fact that having IBD triples the risk of developing colorectal cancer. The fingerprints of the “culprit” are increasingly being seen at the site of every chronic, non-infectious disease epidemic and, ironically, it is a microbial fingerprint: that of an off-kilter gut biome.
The gut biome is a consortium of microbes (mostly bacteria, with some archaea, viruses, fungi, and eukaryotes) that occupy the gut. This biome evolved alongside us and our diet. (A study that examined microbial DNA from paleo feces found entirely new microbial species!)
The mix of species within the biome varies by age between herbivores and omnivores, and the constitution changes seasonally and even reflects circadian patterns. In short, this vital “organ” is affected by climate, by changes in climate and, as we will see, affects how we respond to stress, including a changing climate.
To understand that last point in depth, let’s turn to evidence from three historical experiments.
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In a classic 2004 study, Dr. Nobuyuki Sudo of Kyushu University in Japan and colleagues found that mice raised without the gut microbiome (“germ-free” or GF mice) produced a larger hormonal response when placed in a small container. They had increased stress-hormone levels in their blood compared to mice with “normal” guts.
The study ruled out any influence of maternal care and rearing conditions, leaving only differences in the gut. But this hyperresponse was selective: When rats were exposed to ether, both types of rats responded similarly; It was only when evaluating the severity of a threat required higher-order thinking that stress-hormone levels exploded, suggesting that the microbiome tunes how the brain interprets stressors and regulates the response.
The researchers found that this difference has its roots in brain biology.
GF mice had lower levels of brain-derived neurotrophic factor (BDNF), a molecule essential for forming and maintaining neural connections, especially in areas that shape memory, emotion and stress regulation. GF mice also expressed fewer glucocorticoid receptors, receptors that detect stress hormones and provide an “off switch,” telling the brain and pituitary that enough cortisol has been released. In other words, without the microbiome, the stress systems of GF mice were likely to overreact and shut down slower.
The key detail in this classic study came when scientists introduced the “good bacteria” Bifidobacterium infantis into GF mice during a critical developmental period. Now, stress responses returned to “normal” in these mice. Meanwhile, when GF mice were given, for lack of a better term, “bad bacteria” like Escherichia coli, their stress response became even more exaggerated. The study clearly showed that gut microbes, and the types of gut microbes, mold the way the brain “fires” in response to psychological threat.
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But how did the microbes in the gut “talk” to the brain?
Part of the answer came in a landmark 2011 study in which Javier Bravo and others showed the role played by the vagus nerve. This nerve, whose name comes from the Latin word for “to wander”, originates in the brain stem, travels through the neck and thorax and up and down the digestive tract, carrying signals of satiety, inflammation and energy metabolism primarily from the gut to the brain. In fact, more than 80% of the fibers from the intestinal wall in the vagus are afferent, which means they conduct signals to the brain.
“Trust your gut” has a biological basis. Like.
In this experiment, scientists fed laboratory rats either a probiotic (a strain of Lactobacillus rhamnosus) or plain broth. When exposed to stress, mice given probiotics (PBM) had lower stress-hormone levels in their blood and less persistent anxiety and depression-like behavior. For example, when rats were placed in a pool of deep water with no way to escape, the PBMs swam longer than rats that drank the broth before giving up. In other tests, they were more exploratory and showed significant differences in the way their brains processed stress biochemically.
But the real information came when researchers cut the vagus nerve of rats. Stress-resilience disappeared in the PBM mice, indicating that the gut microbes were actually sending nerve signals to the brain via the vagus nerve rather than simply releasing signals into the bloodstream.
Think of the vagus as a landline that listens to the gut and whispers encouragement to the brain. (There is also WiFi, but we will discuss that some other time)
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So then, what are these bacteria actually doing in the gut?
This suggests that the intestine delivers much more nutrition than it supplies to the body.
It regulates immunity (which is why research on autoimmune disorders is now being directed here), hormonal and psychological responses to stressors. The small intestine is the workhorse; It is where we absorb 90% of our nutrients and where about 70% of the entire immune system lives, constantly mediating between “friends” (dietary nutrients) and “enemies” (invading pathogens). It also contains more than 100 million neurons – more than the spinal cord. Yes, it turns out you can “feel it in your gut”.
But the small intestine can’t break down the cellulosic bonds in fiber (or most of the polyphenols), which pass into the large intestine, where communities of bacteria go to work, breaking down the fiber into short-chain fatty acids (like acetate, propionate, and butyrate) that do wonders for our bodies: telling us we’re full (including generating GLP-1 hormones), regulating insulin sensitivity, reducing inflammation (tightening the lining of the gut. Including), and how the brain processes stress differently.
The small intestine keeps us alive; The colon helps us live well.
Fiber is at its core. The fiber-rich colon microbiome skews toward beneficial bacterial species that produce short-chain fatty acids and calm metabolic, immune, and psychological responses. When fiber is scarce (or too much glucose is available), the environment promotes harmful species, and toxins leak out of the gut, leading to increased inflammation. The effect is two-way: Inflammation irritates the gut, as does stress.
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What makes some bacteria “good”?
Last year, researchers in China exposed rats for several weeks to varying stressors such as wet bedding, cage shaking, sleep disruption, empty water bottles, and short-term food deprivation. The aim was to gradually destroy the combat capability rather than overwhelm it with a single blow.
The animals were then evaluated in a series of behavioral tests. Anhedonia (aversion to pleasure), a core feature of depression, was measured by examining whether rats no longer liked sugar water because they had lost interest in the reward. Behavioral frustration was assessed using the forced-swim and tail-suspension tests, which track how quickly an animal gives up in an unavoidable situation.
Anxiety, motivation, and self-care were assessed by observing exploratory behavior in risky situations and based on how well the rat prepared itself. Based on the results, the researchers divided the mice into stress-resistant and stress-sensitive groups.
Interestingly, these two groups had markedly different microbiomes.
The stress-resistant mice carried microbial communities enriched in bacteria such as Lactobacillus, Prevotella (a microbiome prevalent in many Indian gut biomes) and Akkermansia, which helped maintain the integrity of the gut barrier. In contrast, stress-sensitive mice preferred other species and developed a leaky colon, which allowed inflammatory signals to reach the brain. There, these signals activated microglia, the brain’s immune cells, triggering excessive pruning of synapses in the hippocampus, a central area of mood regulation and stress control.
Then, transplanting “good” microbes from resilient mice into so-called naïve mice proved to be a gamechanger. These naïve mice then began to display resilience to stress. It appears that bacteria rather than behavior make humans; Or, at least, make a mouse. Or, as is most likely, creates rats and humans.
The tragedy is that most of us don’t get enough fiber.
In these conflicted times, with a changing climate, artificial intelligence, and heated geopolitics, it’s easy to feel overwhelmed, and writing about something as mundane as fiber feels almost esoteric. But as these rats swimming in containers or exploring a maze suspended several feet above the ground show: We can’t make stress go away, but with a healthy microbiome, maybe we can swim a little longer. And maybe, just maybe, that will be enough.
(Mridula Ramesh is a climate-tech investor and writer. Contact us at tradeoffs@climateaction.net. Views expressed are personal)
