Rosa Rubicondior: Refuting Creationism - Who's In Charge, You Or Your Gut Microbes?

Newly Discovered ‘Sixth Sense’ Links Gut Microbes to the Brain in Real Time | Duke University School of Medicine

Creationists like to believe they were created perfectly by a benevolent god. Evolutionary biologists, however, know better — and the latest research shows just how wrong the creationist fantasy really is. It turns out that your appetite isn’t entirely under your control. Instead, it’s influenced — perhaps even partly dictated — by the trillions of bacteria and other microbes living in your gut, which evolved to keep themselves well-fed. If you’re a creationist, that means your “perfect design” includes being manipulated by microorganisms.

To anyone who understands evolution, this will come as no particular surprise; to a creationist who believes they were created perfectly, it will be disturbing news, provoking the most convoluted of mental contortions to cope with the resulting cognitive dissonance.

The gut microbiome — consisting of multiple species of bacteria, archaea, viruses, and other single-celled organisms — has evolved to influence, if not completely control, our appetite. They do this to ensure they get an adequate supply of nutrients.

Symbiosis, of which this is an example, is always something of a tussle between the differing needs of the two partners and can easily tip over into a host–parasite relationship — which is probably what it began as. Ultimately, neither side can do anything other than evolve to meet the survival needs of their 'selfish' genes, because those alleles which are best able to survive and replicate will be those which come to predominate in the species’ gene pool. In the long run, the best solution is usually the mutualistic one: the parasite needs the host and, if it gives something back to the host, it is in the host's interest to tolerate or even accommodate the parasite, so the relationship becomes mutualistic.

In this case, the mutualistic solution is one where our gut microbiome protects us from potentially harmful organisms at the price of surrendering a degree of bodily autonomy to the microbes. Since the mechanism was discovered in mice, it is reasonable to assume that it arose in a common ancestor — either in a stem mammal, a pre-mammalian reptile, or even earlier in our evolutionary history.

An added source of distress for creationists is the fact that one of the signalling proteins with which the bacteria manipulate our brain is associated with the bacterial flagellum: flagellin — part of Michael J. Behe's allegedly 'too complex to have evolved' bacterial flagellum. Taking Behe's claim to its logical conclusion, this research shows that his putative intelligent designer has given bacteria the means to turn us into zombies for their own benefit — so much for 'free will'.

The discovery was made by a team led by Duke University School of Medicine neurobiologists Diego Bohórquez, PhD and M. Maya Kaelberer, PhD, who have uncovered the means by which our gut microbes communicate with our brain — via structures they call neuropods in the gut wall. With the help of receptors called TLR5, these detect the flagellin released when the bacteria feed.

The system works like a car freewheeling downhill with the driver's foot on the brake. Release the brake and the car seeds up; apply it and it slows down. When the bacteria produce more flagellin, this applies the brake and supresses our appetite; when they run low on nutrients, they produce less flagellin and we feel hungry.

What is Flagellin? Flagellin is a protein found in many species of bacteria. It’s the main structural component of the bacteria flagellum — a whip-like tail used for movement, allowing bacteria to swim towards food or away from danger. Think of it as the “building block” for a microscopic outboard motor.

Flagellin molecules are arranged in a helical pattern to form the long, hollow filament of the flagellum. When powered by a tiny rotary motor embedded in the bacterial cell wall, these filaments spin at incredible speeds, propelling the bacterium through liquid.

Why It Matters to Us

For the human immune system, flagellin is a big red flag (pun intended). Special immune receptors, such as Toll-like receptor 5 (TLR5), detect flagellin as a sign of bacterial invasion and trigger defensive responses. This makes it part of the body’s ancient innate immune system.

But flagellin isn’t just about defence — it can also act as a signalling molecule. Some gut bacteria release small amounts of flagellin during feeding. Nerve-linked sensory structures in the gut, called neuropods, detect it and send signals to the brain. This is the pathway discovered by the Duke University team, revealing how microbes influence appetite.

The Evolution Angle

For biologists, flagellin is a triumph of evolutionary tinkering: a simple protein adapted into a complex nanomachine over millions of years. For creationists like Michael Behe, it’s been misused as an example of “irreducible complexity” — allegedly too intricate to have evolved. Ironically, research now shows that the same structure they hail as proof of divine design is being used by bacteria to manipulate the very humans who claim to be “perfectly” made.

Their findings are the subject of an open-access paper in Nature and a news release from the Duke University School of Medicine.

Newly Discovered ‘Sixth Sense’ Links Gut Microbes to the Brain in Real Time
Inside a Duke University School of Medicine discovery of a direct line between the microbiome and the brain that may shape behavior and appetite 
In a breakthrough that redefines our understanding of gut-brain communication, researchers have uncovered a “neurobiotic sense,” a newly identified system that lets the brain respond in real time to signals from microbes living in our gut.
 
The new research, led by Duke University School of Medicine neurobiologists Diego Bohórquez, PhD, and M. Maya Kaelberer, PhD, and published in Nature, centers on neuropods, tiny sensor cells in the lining of the colon.

These cells detect a common microbial protein and send rapid messages to the brain that can help curb appetite and guide decision-making.

But this is just the beginning. The team believes this neurobiotic sense may be a broader platform for understanding how the gut detects microbes influencing everything from eating habits to mood — and even how the brain might shape the microbiome in return.  

We were curious whether the body could sense microbial patterns in real time and not just as an immune or inflammatory response, but as a neural response that guides behavior in real time.

Associate Professor Diego V. Bohórquez, co-senior author
Laboratory of Gut Brain Neurobiology
Duke University, Durham, NC, USA.

The key player is flagellin, an ancient protein found in bacterial flagella, a tail-like structure that bacteria use to swim. When we eat, some gut bacteria release flagellin. Neuropods detect it, with help from a receptor called TLR5, and fire off a message through the vagus nerve a major line of communication between the gut and the brain. 

The team, supported by the National Institutes of Health, proposed a bold idea: that the protein from gut bacteria could trigger neuropods to send an appetite-suppressing signal to the brain—a direct microbial influence on behavior.  

The researchers tested this by fasting mice overnight, then giving them a small dose of flagellin directly to the colon. Those mice ate less. 
  
When researchers tried the same experiment in mice missing the TLR5 receptor, nothing changed. The mice kept eating and gained weight, a clue that the pathway helps regulate appetite.  

The findings suggest that flagellin send a “We’ve had enough” signal through TLR5, allowing the gut to tell the brain it’s time to stop eating. Without that receptor, the message doesn’t get through. 

The discovery was guided by lead study authors Winston Liu, MD, PhD, and Emily Alway, both graduate students of the Duke Medical Scientist Training Program and postdoctoral fellow Naama Reicher, PhD.

Their experiments showed that disrupting the pathway changed how much mice ate. That finding pointed to a deeper link between gut microbes and behavior than once thought.

Looking ahead, I think this work will be especially helpful for the broader scientific community to explain how our behavior is influenced by microbes. One clear next step is to investigate how specific diets change the microbial landscape in the gut. That could be a key piece of the puzzle in conditions like obesity or psychiatric disorders.

Associate Professor Diego V. Bohórquez.

The Wisdom of the Gut 

Bohórquez joined Duke’s faculty in 2015 after discovering neuropods. 

His earlier work showed the cells guide our sugar cravings by distinguishing sugar from artificial sweeteners and relaying that information to the brain in milliseconds. The insight hinted that our food choices are rooted in the gut, not just taste.  
  
Now, the latest study looks at neuropods’ influence on satiety, offering a glimpse into how these tiny cells help regulate, not only what we eat, but how much we eat. 

To track feeding behavior in fine detail, the study team built a custom system called “Crunch Master” that used audio and video recordings to monitor bite-by-bite eating. The tracking confirmed that flagellin reduced food intake.  

The doses of flagellin used in the experiments matched the range naturally found in the guts of mice. That means the gut-brain signaling mechanism likely plays a role in day-to-day regulation of appetite.  

The study focused on flagellin from Salmonella Typhimurium, a well-known pathogen. But not all flagellins are created equal. Different bacteria make different versions. Some are harmful; others are part of the body’s normal microbiome.  

That complexity makes the discovery even more compelling. The previously unknown gut-based sensory system, “neurobiotic sense,” allows the brain to listen closely to a range of microbial cues, each with the potential to influence how we feel, eat, and respond to the world around us. 
“It’s similar to how we use our other senses – sight, sound, smell, taste and touch – to interpret our world,” study authors said. “But this one operates from an unexpected place: The gut.”

Abstract
To coexist with its resident microorganisms, the host must have a sense to adjust its behaviour in response to them. In the intestine, a sense for nutrients transduced to the brain through neuroepithelial circuits guides appetitive choices^1,2,3,4,5. However, a sense that allows the host to respond in real time to stimuli arising from resident gut microorganisms remains to be uncovered. Here we show that in the mouse colon, the ubiquitous microbial pattern flagellin—a unifying feature across phyla⁶—stimulates Toll-like receptor 5 (TLR5) in peptide YY (PYY)-labelled colonic neuropod cells. This stimulation leads to PYY release onto NPY2R vagal nodose neurons to regulate feeding. Mice lacking TLR5 in these cells eat more and gain more weight than controls. We found that flagellin does not act on the nerve directly. Instead, flagellin stimulates neuropod cells from the colonic lumen to reduce feeding through a gut–brain sensory neural circuit. Moreover, flagellin reduces feeding independent of immune responses, metabolic changes or the presence of gut microbiota. This sense enables the host to adjust its behaviour in response to a molecular pattern from its resident microorganisms. We call this sense at the interface of the biota and the brain the neurobiotic sense⁷.

Main
Every organism interprets the world through its senses—its Umwelt^8,9. Although five canonical senses have been extensively studied, emerging evidence has established the neural basis of a gut sense, a sense that constantly assesses stimuli arising from the gut lumen^{1,2,3,4,5,10,11,12}. Nutrients, stretch, and microorganisms are among the most salient stimuli that the gut encounters. In the small intestine, epithelial neuropod cells^1,13,14,15 rapidly detect nutrients and relay the sensory information, through the vagus nerve, to influence an animal’s appetitive choices in real time^{4,16,17,18,19}. Growing evidence suggests that gut microorganisms, which are most abundant in the colon20, substantially modulate feeding behaviour^21,22,23,24, potentially through neuromodulators^25,26,27, immune signals²⁸ and vagal pathways^{23,24,29,30,31,32,33,34}. However, a direct neural circuit through which the host interprets microbial sensory information to adjust its feeding remains unknown.

In the colon, vagal neurons form neuroepithelial circuits with neuropod cells, labelled by the neuromodulator PYY^1,3. These, and other colonic epithelial cells, are constantly exposed to microorganisms, which can be recognized by molecular patterns such as flagellin, collectively known as microbe-associated molecular patterns. Flagellin is a structural component of one of the three most ancient organelles, flagella³⁵, and a protein conserved across bacterial phyla6 that activates the pattern recognition receptor TLR5 (refs. ^36,37). Deleting Tlr5 in all intestinal epithelial cells of mice leads to obesity, metabolic inflammation, and spontaneous colitis²⁸. Furthermore, evidence from immortalized gut cell lines suggests that Toll-like receptors may be expressed by specialized sensory epithelial cells, including those that secrete the satiety-inducing protein PYY³⁸. Here we determined that feeding behaviour is regulated by a previously unrecognized gut–brain sensory modality for microbial patterns. We call this sense, at the interface of the biota and the brain, the neurobiotic sense.

The idea that microscopic bacteria can influence — and perhaps even partially control — something as fundamental as human appetite may be unsettling, but it makes perfect sense through the lens of evolution. Over millions of years, microbes and hosts have co-evolved in a complex arms race of survival and cooperation, ultimately leading to the kind of mutualistic relationship we now see in the gut microbiome.

This discovery exposes yet another layer of complexity in the evolutionary history of life — one that’s both elegant and pragmatic. The organisms that survive aren’t the ones designed for perfection, but those that adapt best to their environments, even if that means influencing the behaviour of larger organisms for their own benefit.

For creationists, however, the implications are more awkward. If we were purposefully designed, what does it say about that designer that it equipped bacteria with the tools to manipulate our behaviour for their own gain? The more we understand the natural world, the more it reveals itself as a product of evolutionary processes — messy, fascinating, and entirely godless.

In the end, science doesn't just give us answers; it gives us perspective — a reminder that we are ecosystems, not engineering projects. And in that humbling view of ourselves, there is far more wonder than anything creationism can offer.

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