The Root Cause – Hindgut Biome & B6

In a healthy horse, the hindgut microbes play a powerful role. They don’t just ferment fibre from hay and stemmy grass – they also produce key byproductions – aka postbiotics (some also call them metabolites), including volatile fatty acids (the horse’s main energy source), essential amino acids, and two crucial B-vitamins: B6 and B12.

But there’s a big difference between the activated forms of B6 and B12 (made naturally in the hindgut) and the synthetic forms often found in feeds and supplements. The activated form is what the horse’s liver needs to do its job.

The liver’s job? (Bio)transformation – converting nutrients into usable forms and toxins into excretable forms. And for that, it relies totally on activated B6.

If the liver doesn’t receive this activated B6 from the hindgut microbes, detoxification breaks down. Toxins build up, circulate in the bloodstream, and begin to store in the body, leading to a cascade of metabolic imbalances.

So what does this have to do with KPU?

KPU stands for Cryptopyrroluria, a multi-metabolic disorder. It begins when the hindgut biome becomes disrupted – often from birth. If a foal doesn’t establish a healthy biome, or if the horse later consumes bulk filler feeds, processed carbs, haylage, or experiences chronic stress, the hindgut’s delicate pH balance can be thrown off.

When pH drops too low – sometimes as low as 1.3 in areas like the caecum – the beneficial fibre-fermenting microbes die off. And when they die, they release endotoxins into the body. (In fact, this is one known cause of endotoxin-related laminitis.)

This is called hindgut dysbiosis – where the bad bacteria outnumber the good, and fibre fermentation suffers. As a result, those vital byproducts – including B6 in its natural, activated form – are no longer produced. Without it, the liver can't properly transform toxins.

A dangerous cascade

With the liver unable to detoxify, toxins stay in circulation. The body then resorts to emergency workarounds – storing toxins away in the soft tissues such as tendons, ligaments, muscle, sheath. The result? A horse with multiple overlapping metabolic disorders, all rooted in the same cause.

That’s KPU - a systemic detox failure caused by hindgut dysfunction.

Put simply, KPU means the liver has lost its natural detox ability. Circulating toxins escape into the body and trigger everything from inflammatory symptoms to hormone imbalance. Owners are often left chasing one issue after another with no resolution in sight.

At the heart of it all – fibre and B6

A horse is a grass-forage fibre-fermenter, plain and simple. Their system relies on long-stemmy forage – the fibre is stored in those stems – to feed the hindgut microbes. These microbes then ferment the fibre, producing energy and the B-vitamins needed for metabolic regulation.

• No fibre = dysbiosis. 
• Dysbiosis = no activated B6 produced as one of those vital byproducts. 
• No activated B6 = detox failure. And from there, KPU begins.

That key molecule? Pyridoxal-5-Phosphate (P5P) – the active form of B6. The “5” refers to the molecular position where phosphate binds, enabling the liver to deactivate harmful toxins – think of P5P as the spark plug for healthy detox function.

The ‘disease of a thousand faces’

KPU is increasingly linked to many modern equine conditions, including:

• EMS/IR

• Laminitis

• Recurrent colic

• Chronic coughing

• Sweet itch

• Mallenders/sallenders

• Persistent faecal water

• Loss of performance

• Even headshaking

It’s called the disease of a thousand faces because it rarely presents the same way twice – but the underlying cause may be the same: compromised detox capacity due to hindgut dysbiosis and B6 deficiency.

The good news? KPU isn’t genetic – though it can be passed from dam to foal if the mare’s biome is already disrupted.

And yes – it is reversible. But this is no sprint. Recovery means fully restoring hindgut stability and function – which can take anywhere up to 1 to 5 years, depending on the severity (to fix Mac - our chronic sweet-itch boy, took 15-months) – so the liver can finally get back to doing its job.

KPU can quite literally begin at birth. The first year of a foal’s life is critical for long-term metabolic health, and much of that hinges on one thing: its mother’s microbiome.

When a foal is born, it begins building its own gut flora through a process called coprophagia – eating their dam’s faeces. If the mare has a healthy hindgut biome, this is a brilliant natural system. But if her microbiome is compromised, the foal inherits that imbalance – and the domino effect begins early.

Fortunately, more breeders are now aware of this. Some are beginning to mix mares with healthy microbiomes in with those who’ve had gut challenges, allowing foals to graze on a more diverse microbial pool and improve their chances of good hindgut colonisation. But when that opportunity is missed, the result can be lifelong vulnerability.

If a healthy microbiome isn’t established early on, the foal’s immune system is compromised almost from day one. That foal becomes a metabolic risk for life.

NB: We cover this topic more deeply on our “Creating the Foal’s Microbiome” page – sadly this tabular editor system doesn’t let us include site links here, but you can find this page from the top navigation bar: Advice Centre > A–Z Equine Condition > Mares & Foals.

A not-so-perfect world

Life would be so much easier if we could simply give horses the same kind of species-appropriate probiotics us humans can take. But sadly, we can’t.

As I type there are currently no probiotic supplements that directly mimic the healthy flora of equine gut microbiome – at least, not ones that introduce beneficial, fibre-fermenting microbes capable of digesting cellulose like a horse is meant to.

In a perfect world, we’d be able to install those ideal microbes right into the hindgut whenever there’s been disruption – helping the friendly bugs out-compete the bad and recreate the microbiome horses evolved to have.

But we’re not there yet. The general thinking is to feed more probiotically - which means adlib hay for the cellulose fibre stored in the stalks.

Can we investigate?

In some cases, yes. If we’re lucky enough to access a horse’s early history, we may be able to spot risk factors – such as whether antibiotics were used in the first six months, whether the foal – or their dam – was fed haylage early on, or whether the dam herself had hidden hindgut dysfunction.

It’s not always possible to go that far back, but when we can, it gives us clues as to how the horse’s gut biome began – and what might be missing now.

KPU develops when long-term hindgut dysbiosis disrupts the natural production of vitamin B6 in its active form, P5P. 

Without this, the liver can't detoxify properly. The solution lies in restoring the hindgut biome: fix the gut, and everything else begins to follow.

Testing options

Here’s the good news: KPU can now be detected through a urine test. It’s early days and not yet widely available, but it does give insight into whether the fermentation process in the hindgut is functioning properly.

The not-so-good news is that, at present, the test is only available in Germany. Samples must be analysed within three days, which makes UK courier timescales challenging. Work is underway to make testing more accessible here, but for now, the main focus remains on restoring hindgut function through a nutrient-supportive programme.

A long-term project

Repairing KPU is never a sprint – it’s a serious marathon. If disruption has been present since birth, recovery will take time and patience. The test itself gives a numbered gradient that can indicate the severity:

• A result of 1 suggests mild disruption. A change in feeding and gut restoration could take one to two years (our own sweet itch pony, Mac, took 15-months).
• Scores between 2 and 4 point to major dysbiosis. Intensive therapeutic support is needed, often taking two to three years.
• A score of 5 or higher indicates long-standing damage. Restoring the hindgut will take at least five years, and the body also needs time to eliminate the backlog of stored toxins.

Seasonal patterns

Another clue is the seasonal nature of symptoms. Many metabolic signs flare in spring and summer, when grass growth is highest, and ease during the winter months. This waxing and waning often mirrors the activity of KPU.

The liver’s most important job is detoxification – converting waste products and toxins into a form the kidneys can excrete. 

In horses with KPU, this vital process is disrupted. To understand why, we need to look at how detoxification works when everything runs smoothly.

The two phases of detoxing

• Phase 1 – Adding the “towbar” Think of it like a jeep and a trailer of hay - you can’t pull the trailer without a towbar. In the same way, toxins arriving in the liver can’t move on until a certain molecule - a functional group (FG) – is attached. The FG acts like the towbar, preparing the toxin for the next step.
• Phase 2 – Attaching the trailer Now the towbar is in place, but the trailer still needs hitching up. For toxins, this is where a second molecule is added to allow the liver to turn the toxin into a complex water-soluble state, ready for excretion via the urine, courtesy of the kidneys/bladder. The catalyst that makes this happen is vitamin B6 in its activated form: Pyridoxal-5-Phosphate (P5P).

Only when the toxin is made water-soluble can the kidneys excrete it through urine.

So: Phase 1 – the FG - adds the towbar. Phase 2 - P5P attaches the trailer. Without P5P, the hay isn’t going anywhere – and neither are the toxins.

Why P5P matters

In healthy horses, P5P production ticks along quietly, thanks to a balanced hindgut biome. Most vitamins are produced by the small intestine (bar vit.C which the liver produces, vit.E from forage or winter supplementation, and vit.D from unrugged bodies, i.e. daylight, sunshine), but B6 and B12 are special – they’re made in the hindgut. Which means their production becomes vulnerable when dysbiosis takes hold.

Synthetic B6 (pyridoxine), commonly added to feeds and many balancers, doesn’t help. It’s inactive, the liver doesn’t recognise it, and it gets excreted unused. Only activated B6 – P5P – can drive Phase 2 detoxification.

Without it, the process stalls after Phase 1. Toxins with their “towbar” attached get stuck in circulation, with the liver left saying: “Now what?”

What happens when detox fails?

When detox stalls, the body falls back on emergency measures. Toxins that can’t be excreted get stored in the body instead – and this is where confusion begins.

• Water-soluble toxins get pushed into connective tissue – tendons, ligaments, muscle, sheath. The body then sends an emergency supply of lymph fluid to dilute them, otherwise when waste product concentration gets too high, the connective tissue starts to die off. This swelling looks like fat pads or cresty necks, often mistaken for EMS/IR where in reality, it’s more likely to be the lymphatic system diluting toxic overload.

• Fat-soluble toxins are stored away into fat tissue, and this is where we can unintentionally make the matter worse, because we assume our horse is getting fat. We think our horse has overindulged so we skinny down their rations to make them drop some weight. Wrong! What we’re actually doing is unintentionally releasing fat-soluble toxins back into the body, which now triggers a vicious cycle – if there’s less fat in the body, there’s less storage room for the fat-soluble toxin storage, so they simply circulate back into the body. 

In short? This is why horses often hold onto fat or lymph pads – it’s a protective mechanism, not just excess weight.

The bigger picture

All of this comes back to the gut–liver–kidney axis. If the hindgut biome isn’t producing P5P, the liver can’t complete Phase 2. Toxins build up, get stored, and trigger a cascade of “mystery” metabolic syndromes.

The only safe solution is to restore the hindgut microbiome and get P5P production flowing again. Only then can the liver get back to doing its job and the horse safely lose those pads without re-toxifying.

Meanwhile, there is another emergency pathway, but it comes at a price. See the next chapter – trace element deficiency.

When the liver’s Phase 2 pathway stalls - due to a lack of P5P (active B6) - the body creates an emergency workaround: it binds Phase 1 toxins to certain trace minerals so they can still be excreted via the kidneys.

But here’s the kicker: this process uses up key minerals, draining the body’s stores and creating false deficiencies in zinc, selenium, sulphur, manganese, and sometimes iron.

Let’s explore what that means for each.

Zinc

Zinc deficiency used to be rare in horses. Copper, yes (our region in Somerset is well known as low-copper), but not zinc. Even with the classic high-zinc/low-copper forage profile seen in hay analyses, we rarely saw true zinc deficiency - maybe a need for micro-dosing at most.

But over the past 3–5 years? A shift. We’re now seeing clear zinc deficiency in bloods - without copper being low. This points to a faulty detox process, where zinc is being used up to bind toxins.

Some suggest testing this by adding zinc, rechecking levels, then removing it to see if levels drop again, but this is a sticky-plaster fix. The goal isn’t to keep topping up zinc - it’s to fix the liver pathway so zinc levels regulate themselves.

Important note: Because KPU is poorly recognised in mainstream veterinary science, many labs have lowered their ‘normal’ zinc reference ranges. If your horse’s levels look “low-normal,” question the result. Ask for reference to historic norms or literature-based ranges, not just lab defaults.

Selenium

Until the 1980s, selenium was considered toxic for horses (based on U.S. soil data). It wasn’t fed - and blood values weren’t tested. But then cattle research into ‘white muscle disease’ in calves revealed low selenium forage as a cause, and suddenly, the dairy cow model was applied to horses.

Cue new blood reference values - set too high - and horses were flagged as selenium-deficient. Over time, ranges were lowered toward more realistic levels (around 40 mcg/L), and true selenium deficiency is now rare.

But here’s the link to KPU:

• Zinc and selenium levels tend to rise and fall together.

• When zinc is low (and used for detox), selenium also gets used up.

• When you restore zinc, selenium use decreases, and blood selenium rises.

Bottom line? Don’t feed extra selenium unless absolutely necessary. It’s toxic in excess. Support the liver, fix the KPU, and selenium levels will normalise naturally.

Sulphur

In healthy horses, sulphur is usually plentiful thanks to forage (rich in sulphur-containing amino acids). But KPU horses use up sulphur reserves to bind and eliminate toxins - creating a hidden deficiency.

This won’t show up in blood tests, but the signs speak volumes: poor skin or coat quality, delayed coat shedding, thinning mane and tail, slow hoof growth, soft soles and weak hoof horn.

These are classic sulphur-deficiency flags, and by extension, potential KPU markers.

Good news: sulphur is easy and safe to supplement via MSM (true sulphur).

Manganese

UK soils are already high in manganese, so true deficiency is unlikely - unless KPU is depleting reserves behind the scenes. Like sulphur, it’s not traceable in bloods.

Be cautious: some feed companies are now marketing “manganese deficiency” as the next big concern. But the added manganese is synthetic and poorly absorbed. Supplementing it isn’t the answer.

Focus instead on the root issue - KPU-driven overuse of internal reserves.

Let’s recap

If your horse shows classic signs like zinc or selenium deficiency on bloods, poor coat/hoof/skin condition, or suspicious improvements after adding zinc, MSM, or both

… then KPU could be the missing piece of the puzzle.

Don’t mask the symptoms with single supplements. Support the liver, restore the detox pathways, and the body will re-balance its minerals naturally.

KPU is often called “the disease of a thousand faces” because it can show up in so many different ways. That’s why it so often goes unrecognised, with symptoms treated in isolation instead of at their root.

This section also ties closely to the liver–kidney connection, so you may also find it helpful to read our Liver & Kidneys page alongside this one (ADVICE CENTRE/A-Z Equine Condition/Liver & Kidneys)

Gut disturbances

Let’s start with the obvious. If you’ve got ongoing faecal water, constant diarrhoea, or a gassy horse, you’ve almost certainly got hindgut dysbiosis – which means P5P deficiency is already a given.

Sure, if you put a healthy horse on lush grass and they get the squits for a few days, no worries - that's simply because lush grass has a high water content. But if it’s continuous? Time to worry.

Skin & hooves

Skin issues are classic KPU territory: sweet itch, eczema, mud fever, cellulitis, relentless itching – and mallenders too.

Hooves 

Hooves tell a KPU story too: weak horn, thrush, white line disease, repeat abscessing, and horses that just won’t stop being footy.

Swelling & musculoskeletal Issues

Unexplained swelling of tendons, ligaments, muscles, sheath or teats? Intermittent lameness that vanishes when the vet arrives, only to reappear days later? Or a horse whose back tension takes 30 minutes of warming up before they can work comfortably?

All classic KPU signs. Remember: connective tissues are toxin storage depots when the liver can’t keep up.

Chronic coughing

Here’s one that often stumps people. Horses develop a nagging cough that doesn’t respond to meds and isn’t typically “allergic.” 

The problem? Without enough sulphur, the body can’t build cysteine, and without cysteine it can’t build the mucous layer that normally traps and clears dust.

Dust irritates the airway directly, and the horse coughs, so we think, “Switch to haylage, it’s dust-free!” Well, yes… but haylage is grass wrapped in plastic, and as we know, any plant product wrapped in plastic will ferment via lactic acid bacteria, which is then ingested by the horse who eats haylage. 

And... lactic acid bacteria is probably the biggest wreckers of the microbiome, which crashes the immune system, and fires up autoimmune allergies to pollen, mould, and insect bites. So what looked like a clever solution just fuels the root problem further.

Meanwhile, many people will say, “But my horse is fine on haylage.” Yes, we hear you, but it can take up to 3-years for the symptoms to start appearing, and once they’re there, you have a marathon reset on your hands to get your horse feeling well again.

Mineral disorders

KPU often hijacks minerals, leading to exostosis (extra bone growth), brittle bones, tooth/bone demineralisation (EOTRH), or unexplained lameness.

The multi-morbid horse

At EquiNatural we see this all the time: the “everything’s wrong” horse. It starts with a tendon rupture, then comes the cough, maybe an abscess, then repeat tendon issues, then laminitis, then faecal water… round and round it goes.

As soon as one problem seems under control, another pops up. Years later, you’ve got a horse with a list of conditions as long as your arm – and nothing helps. This is KPU in action.

Therapy that doesn’t work

Another big giveaway: therapies that don’t work. Pain meds that don’t touch pain. Wormers or vaccines that suddenly trigger laminitis or toxic shock.

 “The meds must be wrong,” you say to your vet. Nope – the problem is the biotransformation process. Without P5P, many pharmaceuticals can’t be activated. They either get excreted unused or remain in the body as toxins. 

Cue the infamous “final straw” reactions, or as one customer recently said to us, “I have a horse that is on so many supplements its driving me mental.” Sound familiar?

Other suspects

Even headshaking is now on the KPU radar, though more research is needed.

And finally – the Big One. Our old friend EMS

Insulin resistance, leptin resistance, pseudo-Cushing’s. You tweak the feed, balance the minerals, add the supplements… yet nothing works. That horse may not just be metabolic – they may be a KPU horse.

Yes, the KPU urine test is still only available in Germany, and tricky to access from the UK. So what can we do in the meantime? 

The key is simple: restore the natural microbiome in the hindgut. Once the microbes are back in balance, they’ll start producing P5P again, and liver detoxification can return to normal.

Hay, hay, and more hay

The only true way to fix the hindgut biome is with fibre. That means hay, 24/7, 365 days a year. Horses need the cellulose fibre from those grass stems to feed and repopulate the beneficial microbes.

• If you’re feeding haylage – forget it.
• If you’re soaking hay for too long (no more than 30-minutes then rinse clean) – forget it.
• If your horse ever runs out of hay, especially overnight in the stable – forget it.

Nothing replaces hay. It is the foundation.

Keep the feedbowl simple, always reminding yourself of "species-appropriate" - as in - what the equine gut is evolved to eat.

In other words, meadow grass forage fibre! A basic meadow grass cob or chaff as the carrier (not alfalfa) works well. Into this, add:

• A mineral balancer with extra zinc

• Salt

• Micronised linseed for omega-3

Note: our VitaComplete provides all this in a convenient 3-in-1.

If haylage has been part of the diet, the gut will also need time to deacidify. Feeding spirulina for a couple of weeks can help – it’s an excellent toxin-binder, working mainly through the liver–bile–intestine route, easing pressure on the kidneys.

What not to feed

This part is crucial. Say no to beet, alfalfa, sugar, pectins, muesli mixes, pellets, treats, and especially anything with pro-inflammatory fillers like wheatfeed, oatfeed, soya, or NIS. 

In short: if it looks like a shiny feedbag full of additives and bulk fillers, it’s out.

The more basic, grassforage fibre-based, and species-appropriate the diet, the faster the hindgut environment will reset. Nothing else will do the job properly.

Need more info?

For more on healthy feeding, see our all-things-feed section from the main menu (ADVICE CENTRE/Feeding our Horses Healthy). This section covers everything from Alfalfa to Haylage, Soya to Straw - all the why's and why-nots, what's really in those feedbags, our own feed regiment, how to manage a fussy eater, and more.

The goal is simple: restore the hindgut–liver–kidney pathway and re-establish natural P5P production. 

Don’t panic though! If working out where to begin feels overwhelming, we’ve made it easier with our one-stop KPU Reset Programme (see our KPU Shop page for details).

Step-by-Step Programme

1. Soothe the gut - We start by calming discomfort and reducing inflammation with DuoBute.
2. Regenerate the hindgut - We now follow with a 1-month course of KPUCOMBO. This helps rebalance pH after acidosis and dysbiosis/SIBO, supports the intestinal lining against leaky gut, and rebuilds the hindgut biome–liver pathway.
3. Support the detox organs - After the hindgut reset, we tonify the detox system – liver, kidneys, lymphatics –  with a 1-month course of LKLCARE, giving the liver and kidneys the extra support they need. 
4. P5P - Continue to feed P5P independently, continuing for at least 6-months.

Recommended extras

Adding WildFed can be a big help. It's nature's natural buffet of prebiotic roughage to nourish the beneficial hindgut colonies and keep the biome stable. 

There’s also more information and advice on the KPU Reset product page - the direct link to our KPU Shop page is at the bottom of this advice page.

Bloodwork clues

For those able to run bloods, here are some markers Dr Christina Fritz has highlighted (translated from German):

• Erythrocytes / Hemoglobin: often low (within normal, but at the low end)
• Zinc: usually low
• Selenium: often below normal, though values down to 40µg/L are fine
• CK (Creatinine Kinase): high (normal <130 U/L)
• LDH (Lactate Dehydrogenase): high (normal <400 U/L)
• Potassium: slightly elevated when CK/LDH are high

Horses with raised CK/LDH often feel stiff daily and take 30–45 minutes to loosen up. In sport horses, this stiffness may be the only clue. In ponies and non-sport horses, you may also see lymph “pads” around the saddlebag area or a thick crest full of lymph.

For glucose testing, use sodium-fluoride stabilised blood. Do not fast the horse; allow hay ad lib for 12 hours before testing. Glucose should be below 4.9 mmol/L (83 mg/dL), with sport horses at the upper end of this range and non-sport horses comfortably below.

Supplements worth considering

If bloods and history point toward KPU, support can begin straight away. Typical additions include:

• Zinc (safe unless fed in massive excess) (included in our VitaComplete balancer)
• MSM (organic sulphur) – up to 15g/day is safe and beneficial (Available in our Nutrients shop page)
• P5P (active B6) and Vitamin B12, both water-soluble so any excess is excreted naturally (available in our Nutrients shop page.

Gut restoration, of course, benefits almost every horse – so it’s a good step regardless.

Note

Our EquiNatural KPU therapy plan is independently developed. While I have studied extensively with Dr Christina Fritz and continue to learn from her, our method may differ from hers.

For the practical next step, see our KPU Shop page for the full programme.