Spore-forming bacteria: Bacillus and co. as probiotics

How probiotics in spore form survive stomach acid, what they do in the gut and where the evidence ends.

How solid is the research? Plausible

That spores survive the stomach and become briefly active in the gut has been shown in humans. There is evidence for individual strains: Bacillus coagulans Unique IS2 in IBS and Bacillus clausii for diarrhoea in children, with a small effect. Most other products and uses are barely studied.

Healthy state

Some bacteria can turn into spores: a resting form with a dried-out core and a thick coat that survives heat, drying, oxygen and acid. The main Probiotics Live microorganisms that are meant to provide a benefit in sufficient amounts. The effect depends on the individual strain. More in the chapter “Using fermented foods well” ones are Bacillus subtilis, Bacillus coagulans (now Heyndrickxia coagulans), Bacillus clausii (now Alkalihalobacillus clausii) and Clostridium butyricum. Bacillus subtilis is also found in Japanese natto. One difference between the groups: Bacillus species cope with oxygen, whereas clostridia are Anaerobes Bacteria that live without oxygen. For strict anaerobes oxygen is even toxic; they make up the large majority of the gut flora. More in the chapter “Anaerobic gut bacteria: why the good ones do not fit in a capsule” and need a low-oxygen environment (more in the chapter on anaerobic bacteria).

The advantage: spores survive storage and stomach acid far better than lactic acid bacteria. In the small intestine some of the spores germinate. This is triggered by nutrients such as amino acids and sugars, in some species also by Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea”. The bacteria become active, multiply briefly and produce enzymes, vitamins and substances against pathogens. Then they move on. After a single dose of Bacillus clausii, researchers found the bacteria alive in stool for up to twelve days, in some people more than they had swallowed. So they multiply in the gut but do not settle permanently.

Spores are not just a trick of supplements. A large share of your own colon bacteria, including many Butyrate A short-chain fatty acid and the main energy source for the cells of the colon wall. It strengthens the barrier and dampens inflammation. More in the chapter “Butyrate and other short-chain fatty acids” producers from the clostridia, form spores themselves. This helps them survive outside the body and reach other people. It also explains why some of these bacteria can survive an antibiotic course better than sensitive relatives. In mice, certain clostridia promoted the formation of calming immune cells; whether this holds in humans is open.

A well-studied mechanism: Bacillus bacteria make fengycins. These substances disrupt the signalling system Staphylococcus aureus uses to coordinate itself. In a study in Thailand, people whose stool contained Bacillus carried no Staphylococcus aureus in the gut.

Clostridium butyricum can make butyrate, the main fuel of the cells lining the colon. The strain CBM588 has been used in Japan for decades. In a small open-label study of 30 people with kidney cancer, those who received it alongside immunotherapy lived longer without the disease progressing (12.7 instead of 2.5 months). Larger studies will have to show whether this holds up.

The spore survives stomach acid, germinates in the gut, becomes briefly active and then moves on.

Disrupted state: causes and effects

The effect depends on the strain, not the species. A Meta-analysis An analysis that combines the results of several studies. It is only as good as the studies it includes. of Placebo A dummy treatment without an active ingredient. Comparing with it shows how much a remedy achieves beyond expectation and chance. -controlled trials found evidence in Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. More in the chapter “The gut-brain axis” for Bacillus coagulans Unique IS2, and better quality of life for strain MTCC 5856. This does not automatically apply to other strains. Many products only name the species, not the strain. Quality matters too: for probiotics in general it has been reported that species, strain or germ count in the product can differ from the label.

Bacillus clausii shortened acute diarrhoea in children by about nine hours across six trials. That is not much. The US gastroenterologists even advise against probiotics in general for acute gastroenteritis in children in North America. In 2020 they saw insufficient evidence for probiotics in IBS in general.

Spores are not automatically good. Spore-formers also include pathogens: Clostridioides difficile A bacterium that can spread after antibiotics and cause severe diarrhoea with its toxins. More in the chapter “After antibiotics: C. difficile and faecal transplants” (diarrhoea after antibiotics), Clostridium perfringens, Bacillus cereus (vomiting and diarrhoea after rice kept warm for a long time) and the botulinum bacterium. Probiotic strains are therefore checked to make sure they carry no toxin genes. That applies to tested strains, not to every powder containing soil bacteria. The same toughness that makes spores useful as a probiotic makes them hard to get rid of as a contaminant in food.

Probiotics are not always harmless. In a small study without a control group, 30 people with brain fog and bloating had all been taking probiotics; many had Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised” and D-lactic acid in their urine. The mechanism: in overgrowth, bacteria in the small intestine ferment sugar to lactic acid, including the D form, which humans can barely break down. It enters the blood and can cause fogginess. If the cleaning wave between meals (MMC) is weak, or the closing muscle between small and large intestine, the ileocaecal valve, lets colon bacteria move up, this has an easier time. After stopping and a course of antibiotics, most felt better. Spores germinating in the small intestine are not exempt from this risk.

In severely ill people, with a central line or a severely weakened immune system, caution applies to all live probiotics, because they can rarely enter the blood. This affects premature babies, older people with illnesses and people on chemotherapy most. Healthy people hardly carry this risk. When a product is taken together with an antibiotic: spores themselves are less sensitive to antibiotics, and some products also use strains that are resistant to certain antibiotics. This depends on the strain and does not apply to all.

The effect is only proven for tested strains. Many products only name the species.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Natto and other spore sources in food Natto contains live Bacillus subtilis spores. Soil on vegetables also supplies spore-formers. Whether this brings health benefits is barely studied, but it does no harm in healthy people. Natto is rich in vitamin K and can interfere with blood thinners such as warfarin; if you take them, talk to your practice first. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Do not leave rice and cooked food standing warm Bacillus cereus survives cooking as a spore and multiplies when rice or pasta stands warm for hours. Cool quickly, refrigerate and reheat only once. This is the flip side of spores and has nothing to do with probiotics. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

In IBS: pay attention to the strain If you want to try it, choose a strain tested in studies, such as Bacillus coagulans Unique IS2 or MTCC 5856. Test for four to eight weeks, note your symptoms and stop again if there is no clear improvement. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1]
For acute diarrhoea in children Bacillus clausii can shorten diarrhoea by a few hours. Drinking and salts matter more. Professional societies disagree about probiotics for children. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2][3]
Spores keep well but are no long-term solution Spores do not settle permanently. Their effect ends shortly after stopping. Fibre and plant variety feed your own gut flora more lastingly. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [4]
Read the label A usable product names genus, species and strain, the germ count at the end of shelf life and the duration for which it was tested. Without the strain you cannot look up whether it was ever studied. Be wary of miracle claims. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Take brain fog and bloating on probiotics seriously If probiotics worsen bloating or a foggy head, stop them and have a doctor check for small intestinal bacterial overgrowth. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5]
In cancer immunotherapy, only in trials Clostridium butyricum CBM588 is an exciting approach but not yet sufficiently tested. Only after discussion with your treatment team. Experimental How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [6]
Ask first if your immune system is weakened During chemotherapy, after a transplant, with a central line, serious illness or in premature babies, ask your treatment team before any live probiotic. The risk is small but real. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [7]

From the community: what people report

Experiences and tips from people with the same problems that come up again and again, but for which there are no meaningful studies yet. They are explicitly not evidence.

Spore product – direct import from Japan

In microbiome, SIBO and long Covid communities the same tip keeps coming up: a Japanese product with Clostridium butyricum, ordered directly from Japan. Many report introducing it slowly and say it helped after a course of antibiotics and with histamine problems. Equally recurring are complaints during introduction: abdominal cramps at too high a dose and softer stool.

Evidence: first hints widespread Reported in: r/Microbiome (Reddit community),r/SIBO (Reddit community),r/HistamineIntolerance (Reddit community),Phoenix Rising (ME/CFS forum)
Spores survive stomach acid – said to work where others fail

It is very widely held that spore-forming Bacillus species survive stomach acid unscathed and therefore work where lactic acid bacteria fail. Anyone who does not tolerate Lactobacillus or Bifidobacterium is recommended spore probiotics in the forums almost reflexively. At the same time some report headaches, cramps and diarrhea during introduction, which is then classed as "die-off".

Evidence: first hints comes up again and again Reported in: r/SIBO (Reddit community),r/Microbiome (Reddit community),r/Supplements (Reddit community),r/Biohackers (Reddit community)

Personal reports can mislead: what helps many people may be a placebo, and what helps one may harm another. Treat them as ideas to raise with your doctor or pharmacist – not as instructions.

In the mood for something completely different? Another one, at random

How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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