Story
Irritable Bowel Syndrome
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In one pass Irritable bowel syndrome (IBS) is a long-running condition in which the belly hurts again and again and bowel habits change along with it: the pain often comes around a bowel movement, stool swings between loose and hard, and it does not settle for months.
Educational content, not medical advice — consult a clinician.
Story path
Chapter 1
What IBS is and how it's diagnosed
Irritable bowel syndrome () is a long-running condition in which the belly hurts again and again and bowel habits change along with it: the pain often comes around a bowel movement, stool swings between loose and hard, and it does not settle for months. Yet tests find no visible damage such as an ulcer, a polyp or a tumor.
Finding no lesion is not the same as having no illness. In IBS the parts are intact but they run wrong. The gut moves too fast, then too slow. The sensors in the gut wall that report how far it has been stretched have had their alarm threshold turned down, so a little gas that someone else would not notice registers as pain for you. And the line that carries messages between brain and gut (the gut-brain axis) is out of tune as well. So a clean set of tests and real pain can both be true.
Doctors first recognize IBS directly from a set of symptom criteria (Rome IV), then run a few targeted tests to rule out dangerous disease. Some signs do not look like IBS: blood in the stool or black stool, weight loss you cannot explain, pain that wakes you at night, or symptoms that first appear after age 50. If you have any of these, see a doctor right away and get checked by a gastroenterologist.
Finding no lesion is not the same as having no illness. In IBS the parts are intact but they run wrong. The gut moves too fast, then too slow. The sensors in the gut wall that report how far it has been stretched have had their alarm threshold turned down, so a little gas that someone else would not notice registers as pain for you. And the line that carries messages between brain and gut (the gut-brain axis) is out of tune as well. So a clean set of tests and real pain can both be true.
Doctors first recognize IBS directly from a set of symptom criteria (Rome IV), then run a few targeted tests to rule out dangerous disease. Some signs do not look like IBS: blood in the stool or black stool, weight loss you cannot explain, pain that wakes you at night, or symptoms that first appear after age 50. If you have any of these, see a doctor right away and get checked by a gastroenterologist.
Red flag · Symptoms that do not look like IBS
These symptoms aren't — see a doctor immediately:Blood in the stool, or black stoolUnexplained weight loss (more than 5% in 6 months)Abdominal pain that wakes you at nightDifficulty swallowing that keeps getting worsePersistent high feverSymptoms that first appear after age 50A family history of colorectal cancer or Iron-deficiency anemiaFecal calprotectin above 100 µg/g
Any one of these calls for a gastroenterology visit, a colonoscopy and further imaging.
What some of these terms mean: unexplained weight loss is losing more than 5% of your body weight over half a year without trying to. Calprotectin is a protein that white blood cells leave in the stool when the gut wall is inflamed, so a high value points to inflammation in the gut. IBD is inflammatory bowel disease, which covers ulcerative colitis and Crohn's disease.
Without these red flags, fewer tests are needed. The approach in the ACG 2021 guideline: for a younger person with no red flags, symptoms that meet Rome IV and normal basic blood tests, routine colonoscopy or imaging is usually not needed; the age at which colonoscopy starts follows your local colorectal-cancer screening age. A colonoscopy just to make sure it isn't IBD is usually unnecessary too.
Over-testing has its own costs. It creates anxiety, wastes health-care money, and turns up incidental findings that do not affect your health but lead to still more tests.
Mechanism · No lesion found, yet it really hurts
The gut wall holds a layer of stretch receptors. They do not care what you ate; they only track how far this stretch of bowel has been pushed open. When gas, stool or water stretches the wall, they fire in proportion to the stretch.The signal travels a fixed route. It runs along the nerves that carry messages from the gut to the spinal cord (visceral afferent nerves) into the dorsal horn, the back part of the spinal cord, where it passes to a new neuron. From there it climbs through the brainstem and thalamus into the brain, where two sets of regions split the work. One set works out where it is and how strong it is. The other (the anterior cingulate, the insula and nearby areas) works out how unpleasant it is and whether to tense up.
A healthy gut has a wide no-alarm zone on this route. The gas and movement from an ordinary meal stretch the wall far below the threshold, so the signal is damped in the dorsal horn and never rises to a level you can notice. Your gut is moving all day and you feel nothing — not because there is no signal, but because this gate holds it back.
In many people with (not all of them), studies have measured problems at both ends of this route at once. One way to test it is to inflate a small balloon slowly in the rectum and note the volume at which it starts to hurt.
The outer end, a lower threshold: the receptors in the gut wall and the nerves attached to them become easier to excite, so the same stretch sends a denser signal.The central end, more amplification: the gate in the dorsal horn loosens and lets through signals that should have been damped, and the brain regions that handle how bad it feels (the anterior cingulate and the insula) respond more strongly to the same signal.
Add the two together and the result is this: the same volume of gas that someone else feels as mild bloating is pain for you. That is not you being more delicate; the signal on this route really has been amplified.
One analogy worth borrowing is sunburned skin. A light tap normally feels like nothing; after a sunburn, a tap of the same force makes you jump. The hand did not get heavier; the threshold of the skin's reporting line changed. Borrow only that one point. Sunburn is visible damage that heals in days, whereas an IBS gut has no visible damage, yet its threshold can stay low for a long time.
With this piece in place, three things that look unrelated share one explanation:
Why Rome IV asks how the pain relates to bowel movements: a bowel movement empties what was stretching the wall. The stretch drops, the low-threshold route often goes quiet for a while, and many people feel some relief afterward. Rome IV words it as related to defecation, and pain that gets better or worse after a bowel movement both count, because pain that follows what is in the gut is the mark of this kind of pain.Why low helps IBS: it cuts the gas and water that reach the inside of the gut, which is the volume that stretches the wall. For someone with a normal threshold, trimming that volume makes little difference; for someone whose threshold has dropped, pushing the stretch back under it means less pain.Why psychological treatment can help too: cognitive behavioral therapy () and gut-directed hypnotherapy change how the central end of this route handles the signal. The signal from the gut stays the same, but the brain regions that process it react less, so less pain reaches awareness. The ACG 2021 guideline suggests (a conditional recommendation) gut-directed psychological therapy to improve overall IBS symptoms. This is not the same as it's all in your head: the route is real; one end of it simply sits in the brain.
Clinical · What the Rome IV criteria are asking
When a doctor makes the diagnosis, they follow the Rome IV criteria (2016). It is not a casually assembled list. Every item is really asking the same thing: does your pain follow what is happening inside your gut?The core condition is recurrent abdominal pain on at least 1 day a week on average, present over the last 3 months (with the first symptoms at least 6 months ago), plus at least 2 of the following:
Related to bowel movements (pain that eases or worsens afterward both count)Linked to a change in how often you have bowel movementsLinked to a change in what the stool looks like
Why these three: they all ask whether the pain changes with the volume and forward push inside the gut. If it does, the pain most likely comes from the wall-stretch route. If it does not, the cause should be looked for elsewhere, such as the abdominal wall, the pelvis or the bile ducts. The bar of at least one day a week, for several months has a reason too: it separates a short spell of discomfort after food poisoning or a stomach bug from a route whose threshold has been turned down for a long time.
Next comes the subtype, based on stool form. Stool form is recorded with the Bristol stool scale, a chart that runs from separate hard lumps all the way to mushy and watery stool; the proportions are counted over the bowel movements that are abnormal:
-D (diarrhea type): more than 25% loose or watery, less than 25% hardIBS-C (constipation type): more than 25% hard, less than 25% loose or wateryIBS-M (mixed type): both loose or watery and hard above 25%IBS-U (unclassified): fits none of the above
The subtype is not a label for its own sake; it is how you pick the tool. The same oversensitive route combined with fast transit gives the diarrhea type, and combined with slow transit gives the constipation type. So the drugs on the two sides point in opposite directions (constipation-type drugs promote secretion and movement, diarrhea-type drugs damp contractions), while the desensitizing tools on both sides (low-dose tricyclic antidepressants and psychological therapy) are shared. Get the subtype wrong and the drug pushes symptoms to the other extreme.
One more point that is often missed: the subtype is based on stool form while off medication. If you already take laxatives or antidiarrheals long term, the effect of the drug has to be allowed for, or you will be sorted into the wrong subtype.
Clinical · What to rule out first, and why
First, a widely repeated and costly claim needs correcting: is not a diagnosis of exclusion.Many people, including a lot of popular health writing, say IBS can only be diagnosed once every other disease has been ruled out. The conclusion listed first in the ACG 2021 guideline's summary says the opposite: it suggests a positive diagnostic strategy rather than a strategy of exclusion, and the reason is stated plainly: to shorten the time to the right treatment.
Here is the difference. A positive strategy recognizes IBS directly from the symptom criteria (Rome IV), then runs a few targeted tests to rule out dangerous disease. An exclusion strategy works through every disease anyone can think of, and only what is left is called IBS. The second sounds more careful, but it keeps people stuck in testing, and that is one reason the journey from first symptoms to a diagnosis takes 4 years on average.
So the order is: if you meet the symptom criteria and have no red flags, treatment for IBS can start, alongside the limited work-up below.
The main diseases to rule out are inflammatory bowel disease (, meaning ulcerative colitis and Crohn's disease), lactose intolerance and celiac disease, colitis that is only visible under a microscope (microscopic colitis), and colorectal cancer. The usual tests are:
Basic blood tests: a (CBC), C-reactive protein (), celiac antibodies (tTG-IgA) and thyroid-stimulating hormone ()Stool: occult blood, plus calprotectin whenever there is diarrhea. ⚠️ The guideline's condition is diarrhea, with no age threshold. Writing it as only test after 40 misses the people who need it most: IBD most often starts between ages 15 and 35Colonoscopy: when there are red flags or a family history, or once you reach your local colorectal-cancer screening age
What each test guards against:
CBC and CRP: they check for anemia and whole-body inflammation. IBS does not cause whole-body inflammation, so if inflammatory markers rise, there is real immune activity burning in the gut wall and the search should turn toward IBD.Celiac antibodies (tTG-IgA): celiac disease is an immune reaction to gluten that flattens the villi lining the small intestine. Its symptoms can look exactly like IBS, but it is structural damage and is treated completely differently. Timing matters even more: this test has to be done before starting low . Low FODMAP also cuts wheat, the antibodies may then turn negative, and the diagnosis becomes hard to confirm. A celiac reaction to wheat is also easy to mistake for a FODMAP reaction to the fructans in wheat.TSH: thyroid hormone directly sets how fast the gut moves things along. Too little thyroid hormone (hypothyroidism, when TSH is usually high) causes constipation; too much (hyperthyroidism, when TSH is usually low) causes diarrhea. One blood test can spare months of trial and error with food.Fecal calprotectin: a protein that white blood cells (neutrophils) leave behind when they move into the gut. A high value means inflammation at the level of the cells lining the gut; a normal value pushes IBD well down the list. It is the cheapest step for telling a functional problem from an inflammatory one.
What remains once these are cleared is the invisible but real oversensitive route.
Numbers · Why diagnosis often takes years
First, how common it actually is, because you will see figures in different places that differ by a factor of two.The difference is not the population; it is which version of the criteria you count with. In the Rome Foundation's survey across 33 countries, in its internet-survey arm, the same respondents came out at 4.1% under Rome IV and 10.1% under the looser Rome III. This story uses Rome IV throughout, so the figure here is about 4%; the global 5–10% you often see elsewhere is a figure from the Rome III era. Women are affected about 2 times as often as men. Counted across the population, under either version, it is more common than many digestive diseases that sound more serious.
Yet from first symptoms to diagnosis, the delay averages 4 years.
This is how those years get used up:
On the patient's side: about 50% of patients never see a doctor about it. The symptoms come and go, waiting it out seems to work, and it is hard to talk about, so it is easy to file under something I ate or stress.On the pharmacy side: about 60% treat themselves with over-the-counter drugs without lasting effect. The reason is the subtype: an off-the-shelf antidiarrheal or laxative only presses down the end that is showing right now, and never reaches the route whose threshold was turned down, so it helps a bit, then comes back when you stop, and the cycle runs for years.On the clinic side: with no single test that confirms it, doctors can also slip into ruling things out without naming anything. To a patient, we didn't find anything often sounds like you're not ill, so they leave with neither a diagnosis nor a plan.
Those years are not just time spent waiting. Abdominal pain that goes unexplained for a long time keeps loading the oversensitive route, and anxiety is itself one of the things that turns up the response at its central end, so never getting a diagnosis makes the illness harder to manage. Put the other way round, getting a clear name and a mechanism that makes sense is itself the first step of treatment.
Chapter 2
Low FODMAP · 3 phases
is not one substance. It is the umbrella name for a group of short-chain carbohydrates the small intestine does not fully absorb: the fructans in wheat, onion and garlic, the lactose in milk, the extra fructose in honey and apples, and the sorbitol in sugar-free gum all count.
Whatever the small intestine fails to absorb passes into the large intestine unchanged, where it does two things. Gut bacteria ferment it and make gas. And because the molecules are small and osmotically active, they pull water into the gut. Gas plus water stretches that section of bowel.
That stretch happens to everyone; what differs is the alarm threshold of the gut wall. Someone with a normal threshold does not feel it. For someone with , whose threshold has been turned down, the same stretch crosses the line, so after the same meal another person feels a bit bloated and you feel pain. Low FODMAP cuts exactly that amount of stretch, which is why it helps IBS and means little for people without IBS.
The ACG 2021 guideline gives low FODMAP a conditional recommendation based on very low-quality evidence, and what it recommends is a time-limited trial. It is a three-step process for finding your triggers, not a diet for life.
Whatever the small intestine fails to absorb passes into the large intestine unchanged, where it does two things. Gut bacteria ferment it and make gas. And because the molecules are small and osmotically active, they pull water into the gut. Gas plus water stretches that section of bowel.
That stretch happens to everyone; what differs is the alarm threshold of the gut wall. Someone with a normal threshold does not feel it. For someone with , whose threshold has been turned down, the same stretch crosses the line, so after the same meal another person feels a bit bloated and you feel pain. Low FODMAP cuts exactly that amount of stretch, which is why it helps IBS and means little for people without IBS.
The ACG 2021 guideline gives low FODMAP a conditional recommendation based on very low-quality evidence, and what it recommends is a time-limited trial. It is a three-step process for finding your triggers, not a diet for life.
Myth · Should low FODMAP be for life?
In the ACG 2021 guideline, low is a conditional recommendation based on very low-quality evidence. It is also the one most often misused: most low FODMAP failures come from doing it the wrong way, not from the method itself.The commonest mistake is treating it as a lifelong diet and staying stuck in the strict first phase. That is exactly what the protocol is not meant for:
Phase 1 (strict elimination) is a diagnostic tool, not the end point of treatment. Its only purpose is to see whether symptoms improve. About 70% of patients do; that figure comes from Gibson's 2017 review (which pooled six randomized trials and clinical experience), not from the Halmos 2014 trial. The phase is hard to sustain, and staying in it long term risks poor nutrition, anxiety and social strain. It should last only 2–6 weeks.The real treatment is Phase 2 (systematic reintroduction). Each week you bring back one FODMAP group, starting small and building up, to find your own trigger foods and how much of them you tolerate. Most people find they react to only 2–3 of the groups, not all of them.The phase you can keep up long term is Phase 3 (a personalized diet). You avoid only your own triggers and eat the tolerated foods as usual. It is far richer in nutrients and far less of a mental burden than Phase 1.
One more idea to correct: most high-FODMAP foods (onion, garlic, apples, whole grains, legumes, milk) are very healthy, not "bad foods". People with are sensitive to FODMAPs; FODMAPs are not toxic. So people without IBS should not go low FODMAP; it only cuts out a batch of beneficial foods for nothing.
What makes it actually work:
Find a dietitian trained in FODMAPs. The three phases are hard to get right on your own.Use the FODMAP app from Monash University, where the diet was developed, to look up food ratings. It is the most widely used tool.Treat the whole process as a 3–6 month project to find your triggers. The end point is a personalized everyday diet, not an ever-shrinking list of banned foods.
If you finish the full protocol and still have not improved, stop grinding away at food and look again at other causes: small intestinal bacterial overgrowth (SIBO), microscopic colitis, or anxiety driving the symptoms. Do not keep stretching out the elimination phase.
Mechanism · What each FODMAP letter names
is a string of initials: Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols. Take it apart and you find that these groups escape absorption for different reasons, which is exactly why reintroduction has to go one group at a time.O · oligosaccharides: fructans (wheat, onion, garlic) and galacto-oligosaccharides (GOS, plentiful in legumes). The human small intestine has no enzyme at all that can split them, so nobody absorbs them and everyone ends up feeding them to the bacteria in the large intestine. The difference is not whether you can absorb them, only whether your gut wall is sensitive to the gas that follows.D · disaccharides: lactose (in dairy, especially noticeable in people with lactose intolerance). It has to be split into two simple sugars by lactase, an enzyme at the tips of the small-intestine villi, before it can enter the blood. In people whose lactase has declined with age, unsplit lactose travels on to the large intestine and takes water with it.M · monosaccharides: excess fructose (honey, apples, high-fructose corn syrup). Fructose enters the blood through a dedicated fructose channel in the small intestine. There are only so many of these channels and they fill up easily, so the problem is excess fructose; eaten together with glucose, fructose is actually absorbed more easily.P · polyols: sorbitol and mannitol (sugar-free gum, cherries, mushrooms). They have no dedicated transporter and can only seep slowly through the gaps between cells, so absorption is slow and incomplete. The part left inside the gut is osmotically strong and pulls in water especially hard.
These are not bad foods. Most of the foods above are very healthy (onion, garlic, apples, whole grains, beans, milk). People with are sensitive to FODMAPs; FODMAPs themselves are not toxic. People without IBS should not go low FODMAP; it only cuts out, for no reason, a batch of foods that feed the gut microbiota.
One more point that is often missed: these groups add up. An apple on its own is fine, and a glass of milk on its own is fine, but a meal that brings fructose, lactose and fructans together adds the stretch up. So how much you eat and what you eat it with is often closer to the truth than whether this food is allowed.
The evidence for the diet starts with the Halmos 2014 randomized crossover trial in *Gastroenterology* (the same people with IBS ate a low-FODMAP diet and a typical Australian diet in turn, each acting as their own control), followed by several .
In practice · What each of the three phases solves
Monash University's protocol splits the process into three stages, and each stage solves a different problem.Phase 1 · Strict elimination (2–6 weeks)
Strictly avoid all high- foods.The point is a subtraction experiment: push the fermentable load reaching the gut as low as it will go, and see whether pain and bloating fall with it. About 70% of people with improve clearly. That rate comes from Gibson's 2017 pooling of six randomized trials plus clinical experience; it is not a figure the Halmos 2014 trial itself reports. That trial reported total symptom scores (out of 100: 22.8 on the low-FODMAP diet and 44.9 on a typical Australian diet) and never reported how many people improved.Improvement is itself information: it tells you that your symptoms really are tied to the volume inside the gut rather than coming from somewhere else.It is not a plan for life. This phase is a narrow way to eat and socially costly, and staying in it long term carries nutritional risk. The commonest failure is exactly getting stuck in Phase 1.
Phase 2 · Systematic reintroduction (6–8 weeks)
Each week, bring back 1 FODMAP group, starting with a small amount and building up.The point is to find your own trigger groups and how much of them you tolerate. The four FODMAP groups escape absorption for different reasons: you might be held back by lactase, or by the fructose channel, and you cannot tell which without trying one group at a time.Building the dose up slowly is the key to this phase. For most people the question is not whether they can eat it but how much: half an onion and a whole onion are not the same stretch at all.Most people find they react to only 2–3 groups, not all of them.
Phase 3 · A personalized long-term diet
Avoid only your own triggers and eat the FODMAPs you tolerate as usual.This is the phase you can keep up for the long term. It is richer in nutrients than Phase 1 and far less of a mental burden.
What actually decides success
Work with a gastroenterologist and a dietitian trained in FODMAPs. The three phases are hard to get right on your own.Use the Monash University FODMAP app (the official one, about $9, the most widely used) to look up food ratings. It grades by portion size, rather than giving a black-and-white list of allowed and banned foods.Treat the whole thing as a 3–6 month project whose end point is a personalized everyday diet.If you finish the full protocol and still have not improved, do not keep cutting more foods. Look again at other causes: small intestinal bacterial overgrowth (SIBO), microscopic colitis, or anxiety driving the symptoms.
Chapter 3
The gut-brain link and gut bacteria
The gut has its own complete network of nerves, with so many neurons that it is often called a second brain. Between it and the brain in your head runs a two-way line that never switches off: the gut-brain axis.
Day to day, this line does two plain jobs. It reports up from the gut whether it is stretched, whether it is inflamed, and what the bacteria are producing. And it passes down the brain's sense of whether things are safe and how urgent they are, which it uses to adjust movement, secretion and blood flow. In many people with , what has gone wrong is the tuning of this line: the signals going up are amplified, and the stress signals coming down keep pushing the gut wall's alarm threshold lower.
So stress setting off IBS is not overthinking. In studies, stress activates mast cells in the gut wall (immune cells that release histamine), loosens the gaps between the cells lining the gut, and scrambles the rhythm of gut movement, and all of these are measurable changes. It is also because the route is real, with one end sitting in the brain, that the ACG 2021 guideline suggests (a conditional recommendation) gut-directed psychological therapy to improve overall IBS symptoms.
The gut bacteria really are different too, but which change comes first is still unclear.
Day to day, this line does two plain jobs. It reports up from the gut whether it is stretched, whether it is inflamed, and what the bacteria are producing. And it passes down the brain's sense of whether things are safe and how urgent they are, which it uses to adjust movement, secretion and blood flow. In many people with , what has gone wrong is the tuning of this line: the signals going up are amplified, and the stress signals coming down keep pushing the gut wall's alarm threshold lower.
So stress setting off IBS is not overthinking. In studies, stress activates mast cells in the gut wall (immune cells that release histamine), loosens the gaps between the cells lining the gut, and scrambles the rhythm of gut movement, and all of these are measurable changes. It is also because the route is real, with one end sitting in the brain, that the ACG 2021 guideline suggests (a conditional recommendation) gut-directed psychological therapy to improve overall IBS symptoms.
The gut bacteria really are different too, but which change comes first is still unclear.
Myth · Leaky gut, detox and any-probiotic claims
is one of the densest fields for marketing traps. The symptoms are real, and for a long time there has been no single drug that fixes them, which leaves plenty of room for leaky gut, detox and cure-all probiotic pitches. Here is the evidence, point by point.Several ideas with no evidence base:
Leaky gut syndrome: the gut barrier is real and does change in some conditions, but as a standalone diagnosis that explains every symptom and needs a dedicated repair program, it has no evidence base.Candida detox, heavy-metal detox and parasite detox: no evidence base either. A healthy liver and kidneys already clear metabolic waste all the time; there is no toxin that needs a purchased product to flush it.Combined enzyme-and-detox supplements (common among multi-level-marketing brands): these bundle the ideas above into a personalized package. What they charge for is anxiety about chronic illness, not effectiveness.
With probiotics, the real and the fake are mixed together and need separating:
Not just any probiotic works. Probiotic effects depend on the strain. Only a few specific strains (such as *Bifidobacterium infantis* 35624, the multi-strain product VSL#3 and *Lactobacillus plantarum* 299v) have positive results from small randomized trials, and the certainty of that evidence is low. Ordinary yogurt and most cheap over-the-counter multi-strain products have essentially no evidence.How to use them: usually try one for 4–8 weeks, stop if nothing improves, and do not keep taking it indefinitely.Who really needs to be careful: people with acute pancreatitis predicted to be severe should not take them. In the PROPATRIA trial, giving probiotics to these patients more than doubled the death rate in the probiotic group. People whose immune systems are severely weakened are also commonly advised to be cautious. Probiotics are not completely safe, and the more the better.
On fecal microbiota transplantation (FMT, moving the gut bacteria from a healthy person's stool into a patient's gut): in recurrent *C. difficile* infection, randomized trials show it clearly works. In IBS, several randomized trials were negative or only marginal and hard to reproduce, and it is not currently a recommended IBS treatment. Do not get carried along by the idea that swapping in a new set of gut bacteria cures everything.
IBS is real, but what works for it is a set of tools: evidence-based gastroenterology, a dietitian, and psychological therapy when needed. It is not a detox package or a bottle of cure-all probiotics. When you see a complex personalized protocol with recurring fees, it is most likely selling anxiety.
mcrorie-2017-fiber-two-axes
Mechanism · Which lines the gut-brain axis runs on
There is more than one line between gut and brain; four routes are usually described (the chapter Bacteria in the colon in the Digestive System story goes further into the molecular detail):1. The vagus nerve: a long nerve that runs from the brainstem down into the abdomen and carries messages both ways, but it is not symmetrical in its build. About 80% of its fibers are afferent, meaning they run from gut to brain. Note that this is a count of fibers, not a measured flow of signals; the claim you often see that 90% of signals travel from gut to brain mixes the two up. It is the main trunk line along which the gut reports stretched, moving, something is here, and also the line along which the brain sends relax, slow down back to the digestive tract.
2. The stress axis (the hypothalamic-pituitary-adrenal axis, or axis): the brain judges that there is a threat, the hypothalamus sends out an order, and in the end the adrenal glands release cortisol and other stress hormones. These stress signals change how permeable the gut is and the rhythm of its movement; the sudden need to rush to the toilet under acute stress is tied to this line.
3. Immune and signaling molecules: a large share of the body's immune cells live in the gut wall, and when they are activated they release cytokines (such as ). Hormone-producing cells in the gut lining also release serotonin (). These molecules act on local nerve endings and can also enter the circulation and affect the brain.
4. Bacterial products: the short-chain fatty acids () that gut bacteria make by fermenting fiber feed the cells lining the gut and affect the barrier, while changes in bile acids directly change how fast the gut moves things along.
What stress actually does
About 70% of people with also have a history of anxiety, depression or post-traumatic stress disorder (PTSD). That cannot be brushed off with the words psychological problem, because in studies stress acts on the gut in concrete ways. It activates mast cells in the gut wall and makes them release histamine and other substances, which act on the endings of pain nerves and pull their firing threshold down another notch. It loosens the tight junctions between the cells lining the gut, so gut contents that should stay outside reach the immune cells beneath the lining more easily. And it directly scrambles the rhythm of gut movement.
That is why the desensitizing approach works. Cognitive behavioral therapy () and gut-directed hypnotherapy do not change the gut; they change how the central end of this chain handles the signal, so the same input from the gut arrives in awareness as less pain. The difference from just think more positively is that the first has a clear point of action and a measurable effect, while the second only hands the responsibility back to the patient.
Evidence · Microbes, probiotics and fiber: what holds
The gut bacteria themselvesPeople with have a less diverse gut microbiota, fewer anaerobic bacteria, and usually lower levels of *Bifidobacterium* and *Faecalibacterium* too. But the direction of cause is unclear. Whether a shift in the bacteria pushed the gut into IBS, or the changes in movement and secretion that come with IBS reshaped the bacteria, cannot yet be told apart. In the diarrhea type, gut contents move so fast that bacteria have no time to grow; in the constipation type it is the reverse. So when a microbiome test report tells you your gut flora is out of balance, it is mostly describing the result again, not pointing at a cause you can act on.
Probiotics
The key is that effects depend on the strain; not just any kind works. Only a few strains (*Bifidobacterium infantis* 35624, VSL#3 and *Lactobacillus plantarum* 299v) have positive results from small randomized trials, and the certainty of that evidence is low. Ordinary yogurt and most cheap blends have essentially no evidence. Usually try one for 4–8 weeks and stop if nothing improves. Take special care: people with acute pancreatitis predicted to be severe should not take them (in the PROPATRIA trial, Besselink 2008 in *The Lancet*, deaths ×2 in the probiotic group), and people whose immune systems are severely weakened should be cautious.
Fiber: a counterintuitive fork in the road
Soluble fiber (psyllium husk): a common first step for the constipation type, supported by randomized trials (certainty of evidence: moderate). It forms a gel with water and makes stool softer and more slippery by holding on to water, not by pushing with bulk. It also ferments slowly, so it does not release a large burst of gas.Insoluble fiber (wheat bran): can actually make symptoms worse, but not by producing gas. Bran is barely fermented; it travels the whole way intact and irritates the gut lining mechanically (McRorie 2017). On a route whose threshold has already dropped, that mechanical irritation is enough on its own to become pain.So eat more fiber is a risky blanket line for IBS: the two kinds of fiber work by completely different mechanisms, even in opposite directions. High-dose products that mix several fibers are also best avoided.
Fecal microbiota transplantation (FMT)
In recurrent *C. difficile* infection, randomized trials show it clearly works (van Nood 2013, in *NEJM*). That is because the root of that disease is a microbiota wiped out by antibiotics, so putting back a whole ecosystem is exactly on target. In IBS, several randomized trials were negative or only marginal (El-Salhy 2020 is one of the few positive results and has been hard to reproduce), and it is not currently a recommended IBS treatment. The difference comes back to the line above, the direction of cause is unclear: the gut bacteria are probably not the root of IBS, so swapping them out cannot fix the root.
Useless marketing traps
Candida detox and leaky gut syndrome: no evidence baseHeavy-metal detox: no evidence baseParasite detox: no evidence baseEnzyme-and-detox supplements (Plexus, Le-Vel, Beachbody and other multi-level-marketing brands)
Chapter 4
Pitfalls of SIBO tests and drugs
SIBO stands for small intestinal bacterial overgrowth. It describes something quite specific: bacteria that should be sparse in the small intestine grow to numbers approaching those of the large intestine, so fermentation starts early, in a place not built for it.
Why does that matter? The large intestine is wide, can hold contents, and works by fermentation anyway, so its wall is used to it. The small intestine is narrow and long, and its job is to absorb nutrients quietly. When bacteria eat carbohydrates before you can, they take nutrients that should have been absorbed by you, and they make gas on the spot, stretching this narrow tube from the inside. On a route whose threshold has already dropped, that means fullness and pain.
True SIBO exists, and there are clear groups of people who should be tested for it. The trouble is that the test cannot tell: the breath test used most often cannot separate true SIBO from ordinary bloating. That gap is the main foothold of the SIBO clinic business.
Why does that matter? The large intestine is wide, can hold contents, and works by fermentation anyway, so its wall is used to it. The small intestine is narrow and long, and its job is to absorb nutrients quietly. When bacteria eat carbohydrates before you can, they take nutrients that should have been absorbed by you, and they make gas on the spot, stretching this narrow tube from the inside. On a route whose threshold has already dropped, that means fullness and pain.
True SIBO exists, and there are clear groups of people who should be tested for it. The trouble is that the test cannot tell: the breath test used most often cannot separate true SIBO from ordinary bloating. That gap is the main foothold of the SIBO clinic business.
Clinical · What true SIBO looks like
Normally there are very few bacteria in the small intestine: fewer than 10⁵ per milliliter (CFU/mL), compared with 10¹¹ in the large intestine, a gap of several orders of magnitude. The small intestine keeps that gap with three lines of defense. Stomach acid kills most swallowed bacteria upstream. Bile and pancreatic juice slow bacterial growth by themselves. Most important of all is the housekeeping wave between meals, which sweeps from the stomach all the way to the end of the small intestine and, like a scheduled clear-out, drives leftovers and bacteria downstream. If any of the three fails for a long time, bacteria get a chance to settle in the small intestine.SIBO is that settling actually happening: unusually large numbers of bacteria move into the small intestine and ferment where they should not, causing bloating, gas and poor absorption of nutrients.
Who should really be tested (for these people, checking for SIBO makes sense):
Short bowel syndrome (after surgery took out a large part of the small intestine)Disorders of gut movement, such as nerve damage from diabetes (autonomic neuropathy) or scleroderma: exactly the housekeeping wave failingRecurrent diarrhea together with low vitamin B12 and poor fat absorption
Why B12 and fat in particular: these two are not picked at random; they are the fingerprints that bacteria stealing the meal leave behind. Bacteria in the small intestine eat the B12 in food before you can, so the amount you eat stays the same while the amount you absorb falls. They also break bile acids apart early, and fat absorption depends entirely on bile acids emulsifying fat into tiny droplets. With the bile acids broken up early, fat cannot be emulsified and goes straight into the stool. So the combination of diarrhea, low B12 and greasy stool points to true SIBO more strongly than bloating alone.
Among people with , reported SIBO rates range from 30% to 80%. A range that wide is itself a finding. It is not that populations differ so much; it is that diagnostic methods are not consistent: change the test or the cut-off and the rate can more than double. A diagnosis that cannot settle its own rate is not a good place to start spending money.
Myth · Why the breath test cannot tell
The idea behind the breath test (a hydrogen breath test using glucose or lactulose) is simple. You drink a dose of sugar, and every so often the hydrogen in your breath is measured. Human cells do not make hydrogen, so hydrogen in the breath can only come from gut bacteria fermenting something. If the hydrogen rises early, the theory says the sugar was eaten by bacteria before it reached the large intestine, meaning there are bacteria in the small intestine.The problem lies in the word early. It rests on an assumption: that sugar takes a roughly fixed time to travel from the mouth to the large intestine. In many people that assumption fails:
People whose gut moves fast: the sugar reaches the large intestine sooner than expected, so normal fermentation in the large intestine is read as fermentation in the small intestine. These people have no SIBO, yet the test comes back positive.Lactulose gives more false positives than glucose: the body does not absorb lactulose at all, so it is bound to travel all the way to the large intestine and be fermented there. The test is therefore betting on when fermentation happens, not where. Glucose is usually fully absorbed in the upper small intestine, so a positive result with it is more telling, but for the same reason it more easily misses SIBO near the end of the small intestine.
So here is how it actually performs against culturing fluid drawn from the small intestine: sensitivity 50–70%, specificity 60–80%. Sensitivity is the share of people who really have SIBO who test positive; specificity is the share of people without SIBO who test negative. Put plainly, a sizeable share of true SIBO is missed, and a sizeable share of positive results are false. That is not a little imprecise; it is unreliable at the level where you have to make a decision.
The real gold standard is culturing fluid drawn from the small intestine, but that means passing a tube into the small intestine to take a sample. It is invasive and rarely done.
Home SIBO test kits sell for $300–500, and their results cannot tell true SIBO from ordinary bloating either. When a test performs like this even in professional hands, using it at home gives you not information but a positive result that can be used to sell the next program.
Clinical · How much rifaximin helps, and why relapse
After a diagnosis, the drug usually used is rifaximin, an intestinal antibiotic that is barely absorbed.Less than 0.4% is absorbed into the body, which means almost all of it stays inside the gut to work, so side effects across the body are few.Randomized-trial evidence (Pimentel 2011 in *NEJM*, the two phase 3 trials TARGET 1 and TARGET 2): 550 mg three times a day for 2 weeks. On the main outcome, adequate relief of overall symptoms, the rate was 40.7% versus 31.7% on placebo (P < .001). Note that these two trials enrolled people with without constipation, and they were not tested for SIBO before entry. The ACG 2021 guideline gives rifaximin for overall symptoms of diarrhea-type IBS a strong recommendation (moderate-quality evidence).Relapse is common: 40–60% relapse within 6 months, and the drug has to be repeated.Cost: $1500–2000 for a 14-day course (the US price, usually needing insurance approval).
Read those numbers first. The improvement rates on the drug and on placebo differ by only single-digit percentage points. That means most of the improvement in the drug group would have happened on placebo too; the slice that truly belongs to the drug is much smaller than four in ten patients improved makes it sound. It is a genuinely effective drug, but not one that solves IBS in one go. Whether a benefit of this size is worth the money and a round of antibiotics is a sum to work out with your doctor.
Then, why relapse is so common. All an antibiotic can do is push down the bacteria that are in the small intestine right now; it cannot fix whatever let the bacteria move in. The small intestine keeps bacterial numbers low with three lines of defense: stomach acid, bile and pancreatic juice, and the housekeeping wave between meals. If what failed is the housekeeping wave (nerve damage from diabetes, scleroderma, or simply snacking all day so the gut never gets a fasting window to clear out), then once the drug stops, bacteria move back in along the same road.
So taking the drug again and again is not the way out; fixing the cause is. Leave longer gaps between meals so the housekeeping wave has a chance to finish, and treat the underlying movement disorder. That is the direction that brings relapse down.
A few more points. For the type with high methane in the breath (methane-producing SIBO), a combination of neomycin and rifaximin is often used. On diet, during SIBO treatment avoid high- foods (foods rich in short-chain carbohydrates that the small intestine does not fully absorb and that ferment easily) and limit other easily fermented carbohydrates. The reason is the same as for the low-FODMAP diet in IBS: give the bacteria less raw material and they make less gas.
Myth · What SIBO clinics are actually selling
The SIBO clinic business model has a very consistent shape. Recognizing the shape is more useful than memorizing every product name:Skip the Rome criteria and red-flag screening and sell the breath test straight away. The test's false-positive rate is high enough that almost anyone can test positive for something; for a business, that is not a flaw but a selling point.After a positive result, prescribe a personalized, complicated antibiotic or herbal regimen. The more complicated the regimen, the harder it is to tell which step did anything, and the easier it is, when it fails, to put it down to your case is special, you need another round.Herbal antibacterial regimens such as berberine, neem and oregano oil have no randomized-trial evidence, and their safety has not been shown either (see the Berberine story).A 6-month retainer for repeated treatment: billed like care for a chronic disease. A chronic-disease model is not the problem in itself; the problem is that it rests on a diagnosis the test cannot make, so relapse can always be manufactured.
The right path is plain: see a gastroenterologist, test selectively only when there is a reason to, and have a doctor prescribe rifaximin when it is needed.
One way to tell: check whether the plan has an end point. A responsible plan tells you what counts as success and when to stop and change direction. A plan that sells anxiety only ever has a next round.
Clinical · Drugs by subtype, in a supporting role
drugs are not the lead; they fill gaps alongside lifestyle and diet. Choose by subtype. The subtype can guide the choice because the same oversensitive route, combined with different speeds of movement, needs nudging in opposite directions.Constipation type (IBS-C): the main tools are prescription drugs that increase secretion into the gut and speed things through, such as linaclotide, lubiprostone, plecanatide and tenapanor, supported by several large randomized trials (certainty of evidence: high). What they share is pulling water into the gut so its contents soften and move more easily. Note that this is the same physical action as pulling in water; the difference is that one is a controlled dose at a time you choose, and the other happens uncontrolled at meals. A cheap fallback is an osmotic laxative such as polyethylene glycol (PEG), whose evidence is weaker than for the drugs above.Diarrhea type (IBS-D): prescription drugs that adjust gut contractions and stop diarrhea. A pause is needed here: both of the drugs most often named carry hard restrictions; neither is a first-line drug to prescribe casually:Eluxadoline: not to be used by anyone without a gallbladder. The label is blunt: in people without a gallbladder it raises the risk of pancreatitis and spasm of the sphincter of Oddi. Most reported serious cases began within a week of starting, some after only one or two doses, and deaths have been reported. It is also ruled out for people with a blocked bile duct, alcohol misuse or more than 3 alcoholic drinks a day, a past episode of pancreatitis, or severe liver impairment. ACG 2021 gives it a conditional recommendation (moderate-quality evidence).Alosetron: carries a boxed warning for ischemic colitis and serious complications of constipation; these events have led to hospital admission, a few needed a blood transfusion or surgery, and deaths have occurred. Its use is tightly limited: only for women with severe IBS-D, generally present for 6 months or longer, that has not responded to standard treatment. It must be stopped immediately at any sign of constipation or ischemic colitis. ACG 2021 likewise gives only a conditional recommendation (low-quality evidence).For short-term relief, loperamide can stop diarrhea; for stubborn cases, rifaximin as described above.Mainly abdominal pain: this is the group that goes after the oversensitive route itself. Antispasmodics (such as hyoscine and dicyclomine) relax cramping smooth muscle and reduce how much the gut wall tugs on itself (supported by randomized trials, certainty of evidence: moderate). Low-dose tricyclic antidepressants (such as amitriptyline and nortriptyline) work through the nerve-pain pathway, turning the signal down at the nerves in the gut and at the spinal cord. So here they are not being used as antidepressants, and the dose is far below the dose for depression (supported by randomized trials, certainty of evidence: moderate). When anxiety is also present, a selective serotonin reuptake inhibitor () can also be considered.
Note how the three groups divide the work: the first two adjust how fast things move, and the third adjusts sensitivity. Many people take a laxative or an antidiarrheal and find the pain has not improved. That is why: those two groups never touch the pain route at all.
Chapter 5
Where to start, step by step
Put the whole thing on one path: rule out danger first, change daily habits next, and only then turn to diet and drugs. The order cannot be flipped. Dive straight into low , find out months later that it was a different disease, and those months of hardship were for nothing.
If anything on the red-flag list applies, see a gastroenterologist immediately. With no red flags, start at the layer that costs least and has the fewest side effects, and build up from there: regular meals, eating slowly, less alcohol and coffee, a walk every day, and getting stress under control. This layer looks unremarkable, but it works on exactly the gut-brain line.
Only above that comes low FODMAP, and it has to be followed through from elimination to reintroduction; the end point is a personalized everyday diet, not an ever-shrinking list of banned foods. If symptoms persist, see a gastroenterologist about medication and whether SIBO should be checked.
is a real disease, not fussiness. Most people with it can be helped back to a normal quality of life, but it takes several tools working together, not one miracle drug.
If anything on the red-flag list applies, see a gastroenterologist immediately. With no red flags, start at the layer that costs least and has the fewest side effects, and build up from there: regular meals, eating slowly, less alcohol and coffee, a walk every day, and getting stress under control. This layer looks unremarkable, but it works on exactly the gut-brain line.
Only above that comes low FODMAP, and it has to be followed through from elimination to reintroduction; the end point is a personalized everyday diet, not an ever-shrinking list of banned foods. If symptoms persist, see a gastroenterologist about medication and whether SIBO should be checked.
is a real disease, not fussiness. Most people with it can be helped back to a normal quality of life, but it takes several tools working together, not one miracle drug.
In practice · How to start this week
A 4-week self-check, then a 6-month management pathWeek 1 · Check for red flags and see a doctor
If anything on the red-flag list applies, see a gastroenterologist immediately.With no red flags, your family doctor runs the basic tests: a , C-reactive protein, celiac antibodies (tTG-IgA), thyroid-stimulating hormone () and fecal calprotectin.Check yourself against the Rome IV symptom criteria (the Monash University app also explains them).
Weeks 2–3 · Lay the lifestyle foundation
Eat three regular meals and avoid eating a lot at once. A big meal stretches the gut a lot in one go, landing right on the threshold.If you are sensitive, cut down on alcohol and coffee. Coffee directly speeds up movement in the colon, and alcohol makes the gut more permeable.Eat slowly, without a screen in front of you. Eating fast means swallowing more air, and that air also ends up taking space in the gut.Walk for 30 minutes a day to help the gut move.Manage stress: cognitive behavioral therapy, mindfulness, and belly (diaphragmatic) breathing. The diaphragm presses down on the abdomen with each breath, which can be thought of as a gentle massage for the gut, not just relaxation.
Week 4 · If needed, start phase 1 of low FODMAP
Find a FODMAP dietitian.The strict elimination phase lasts 2–6 weeks.Have the Monash University FODMAP app ready.Do not try to do it alone.
Months 2–4 · FODMAP reintroduction
Bring back 1 group per week.Find your own trigger foods.Follow-up with the dietitian.
Month 6 · A stable personalized diet
Avoid your own triggers.Eat the foods you tolerate as usual.No more strict low FODMAP.
If symptoms persist, see a gastroenterologist about medication and whether SIBO should be checked. Do not go to a SIBO clinic; find an evidence-based gastroenterologist and choose drugs by subtype (see Pitfalls of SIBO tests and drugs).
Why it has to be this order: each layer up is more expensive, more trouble and has more side effects than the one below it, and when the lower layers are in place, the upper layers work better. Skip the lifestyle layer and jump straight to low FODMAP, and a common result is a very restricted diet, symptoms only half better, and then the mistaken conclusion that even low FODMAP didn't work.
Background · Where this story connects
If your answers in the health report suggest possible , or raise questions about fiber and gut bacteria, the report brings you back to this story. After reading it, each of the stories below fills in one more piece:The chapter Bacteria in the colon in the Digestive System story: how short-chain fatty acids are made, and how the gut-brain axis passes messages at the molecular level.Probiotics: which strains have evidence, and why most swallowed bacteria do not survive stomach acid.Carbs & Fiber: why soluble and insoluble fiber push in opposite directions.Insomnia: how poor sleep and the stress axis (the axis) push the gut toward greater sensitivity.Berberine: where the evidence really stands for the kind of herbal regimen SIBO clinics most often prescribe.
Steer clear of marketing routes such as SIBO clinics, candida detox and leaky gut syndrome. Find evidence-based gastroenterology and a dietitian, with psychological therapy when needed.
References · 13
- Lacy, B. E., Mearin, F., Chang, L., Chey, W. D., Lembo, A. J., Simren, M., & Spiller, R. (2016). Bowel disorders (Rome IV criteria). Gastroenterology, 150(6), 1393-1407. 10.1053/j.gastro.2016.02.031
- Lacy, B. E., Pimentel, M., Brenner, D. M., Chey, W. D., Keefer, L. A., Long, M. D., & Moshiree, B. (2021). ACG clinical guideline: management of irritable bowel syndrome. The American Journal of Gastroenterology, 116(1), 17-44. Graded recommendations include a positive diagnostic strategy over one of exclusion (strong, high quality), a limited trial of a low-FODMAP diet (conditional, very low quality), rifaximin for global IBS-D symptoms (strong, moderate quality), mixed opioid agonists/antagonists such as eluxadoline (conditional, moderate quality), and alosetron for women with severe IBS-D who have failed conventional therapy (conditional, low quality). Grades checked against the full-text Table 2 (2026-09-24); the abstract's verbs do NOT map onto grades. There are TWO positive-diagnosis statements: 'We recommend a positive diagnostic strategy ... to improve cost-effectiveness' (strong, high quality) and 'We suggest a positive diagnostic strategy ... to improve time to initiate appropriate therapy' (consensus, unable to assess using GRADE) - the abstract quotes only the second. The low-FODMAP trial is worded 'We recommend' yet graded conditional, very low quality. Other grades: rifaximin strong, moderate; chloride channel activators for IBS-C strong, moderate; guanylate cyclase activators strong, high; tricyclic antidepressants strong, moderate; soluble fibre strong, moderate; peppermint conditional, low; gut-directed psychotherapies conditional, very low; against probiotics conditional, very low; against antispasmodics conditional, low; celiac serology in IBS with diarrhoea strong, moderate (full text Table 2, publisher PDF hosted by the ACG). 10.14309/ajg.0000000000001036
- Sperber, A. D., Bangdiwala, S. I., Drossman, D. A., Ghoshal, U. C., Simren, M., Tack, J., et al. (2021). Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology, 160(1), 99-114.e3. Across 33 countries, IBS prevalence was 4.1% under Rome IV criteria versus 10.1% under the looser Rome III criteria in the Internet survey (1.5% vs 3.5% in the household survey) — the criteria version, not the population, accounts for most of the spread between commonly quoted prevalence figures. 10.1053/j.gastro.2020.04.014
- Halmos, E. P., Power, V. A., Shepherd, S. J., Gibson, P. R., & Muir, J. G. (2014). A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology, 146(1), 67-75. Randomized controlled cross-over trial; a low-FODMAP diet significantly reduced overall IBS symptoms versus a typical Australian diet. Onion and garlic are among the highest-fructan (FODMAP) foods. 10.1053/j.gastro.2013.09.046
- Tuck, C. J., Reed, D. E., Muir, J. G., & Vanner, S. J. (2020). Implementation of the low FODMAP diet in functional gastrointestinal symptoms: a real-world experience. Neurogastroenterology & Motility, 32(1), e13730. 10.1111/nmo.13730
- Gibson, P. R. (2017). The evidence base for efficacy of the low FODMAP diet in irritable bowel syndrome: is it ready for prime time as a first-line therapy? Journal of Gastroenterology and Hepatology, 32(S1), 32-35. Six RCTs comparing the low FODMAP diet with placebo approaches were uniformly positive; real-world experience confirms that about 70% of patients respond, and the author concludes a dietitian-led low FODMAP diet should be considered a first-line therapy in IBS. 10.1111/jgh.13693
- van Nood, E., Vrieze, A., Nieuwdorp, M., et al. (2013). Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England Journal of Medicine, 368(5), 407-415. Stopped after an interim analysis. Duodenal infusion of donor feces (after 4 days of vancomycin and bowel lavage) resolved recurrent C. difficile diarrhea in 13/16 (81%) after the first infusion, and in 2 of the remaining 3 after a second donor; vancomycin alone 4/13 (31%), vancomycin with bowel lavage 3/13 (23%) (abstract, PMID 23323867). 10.1056/NEJMoa1205037
- Suez, J., Zmora, N., Zilberman-Schapira, G., et al. (2018). Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell, 174(6), 1406-1423.e16. After antibiotics, a multi-strain probiotic colonized the human mucosa more readily but induced a markedly delayed and persistently incomplete reconstitution of the native stool and mucosal microbiome and host transcriptome compared with spontaneous recovery, whereas autologous fecal microbiome transplantation gave a rapid, near-complete recovery within days (abstract, PMID 30193113). 10.1016/j.cell.2018.08.047
- Besselink, M. G., van Santvoort, H. C., Buskens, E., et al. (2008). Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial (PROPATRIA). The Lancet, 371(9613), 651-659. 298 patients with predicted severe acute pancreatitis given a multispecies probiotic or placebo enterally for 28 days. Infectious complications 30% vs 28% (RR 1.06). Deaths 24 (16%) vs 9 (6%), RR 2.53 (1.22-5.25); bowel ischaemia in 9 probiotic patients (8 fatal) vs none. The Lancet later published an expression of concern about this paper (Lancet 2010;375:875-6) (abstract, PMID 18279948). 10.1016/S0140-6736(08)60207-X
- Bonaz, B., Bazin, T., & Pellissier, S. (2018). The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in Neuroscience, 12, 49. The vagus is a mixed nerve about 80% afferent (gut/viscera to brain), a principal bidirectional pathway of the gut-brain axis. 10.3389/fnins.2018.00049
- Pimentel, M., Lembo, A., Chey, W. D., Zakko, S., Ringel, Y., Yu, J., Mareya, S. M., Shaw, A. L., Bortey, E., & Forbes, W. P. (2011). Rifaximin therapy for patients with irritable bowel syndrome without constipation. New England Journal of Medicine, 364(1), 22-32. Two identically designed phase 3 trials (TARGET 1 and TARGET 2): rifaximin 550 mg three times daily for 2 weeks produced adequate relief of global IBS symptoms in 40.7% of patients versus 31.7% on placebo (P < .001) over the 10-week follow-up. 10.1056/NEJMoa1004409
- U.S. Food and Drug Administration. (2024, July). VIBERZI (eluxadoline) tablets, for oral use, CIV — full prescribing information. Contraindicated in patients without a gallbladder because of an increased risk of pancreatitis and sphincter of Oddi spasm; most serious cases began within a week of starting treatment and some after only one or two doses, and fatal cases have been reported in patients without a gallbladder. Also contraindicated with biliary duct obstruction or sphincter of Oddi disease, alcohol misuse or more than 3 alcoholic drinks daily, prior pancreatitis, severe hepatic impairment, and chronic or severe constipation. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7821bd40-4c84-4984-951b-6436ae20421a
- U.S. Food and Drug Administration. (2019, April). LOTRONEX (alosetron hydrochloride) tablets, for oral use — full prescribing information. Boxed warning: infrequent but serious gastrointestinal adverse reactions, including ischaemic colitis and serious complications of constipation, have led to hospitalisation and rarely to blood transfusion, surgery, and death. Indicated only for women with severe diarrhoea-predominant IBS of generally six months or longer who have not responded to conventional therapy, and it must be stopped immediately if constipation or symptoms of ischaemic colitis appear. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c216e967-436f-475a-8e6a-2ad11adc63af