The gut bacteria that produce histamine in IBS – revealed!
Histamine can be secreted by many bacteria, but the particular microbes responsible for histamine overproduction in the gut have remained a mystery – until now. Read on as I break down the findings from a long-awaited study that uncovers the role of bacterial histamine in irritable bowel syndrome, and the gut bacteria involved!
Histamine is a compound released by immune cells and involved in the local immune response. It is also a known mediator of pain.
In recent years, histamine has become increasingly implicated in irritable bowel syndrome (IBS). It is also thought that the various symptoms characteristic of “histamine intolerance” might be due to an overproduction of histamine in the gut, overwhelming the body’s ability to break down and metabolize histamine.
Now, a new study published in Science Translational Medicine suggests that bacterial histamine can induce abdominal pain in a subset of patients with IBS.1 Moreover, it identifies the bacterium Klebsiella aerogenes as the primary producer of gut histamine!
In this article, I break down these new findings and discuss the implications. First, some quick background to explain the motivation for this latest study.
Low FODMAP diets reduce urine histamine in patients with IBS
Low FODMAP diets have long been recognized for their ability to help mitigate symptoms in patients with IBS. However, the exact mechanism by which these carbohydrates worsen gut symptoms has been unclear.
In 2017, a group of researchers at McMaster University randomly assigned IBS patients to consume a low or high FODMAP diet.2 After the dietary intervention, they measured a variety of metabolites in the urine.
They found that about a third of the IBS patients had high urine histamine levels at baseline, and that urine histamine was 8 times lower after the low FODMAP diet.
Diet – microbiota interactions lead to increased gut sensitivity
Building on these findings in their most recent study, the researchers transplanted the gut microbiota from (1) an IBS patient with high urine histamine, (2) an IBS patient with low urine histamine, and (3) a healthy control subject into three separate groups of germ-free mice.
After a colonization period to allow the microbiotas to take hold in the mice, they further split each group of mice in two, to receive a low or high fermentable carbohydrate diet.
Lo and behold, only the group of mice colonized with the microbiota from the IBS patient with high urine histamine and fed the high fermentable carbohydrate diet had increased gut sensitivity!
Klebsiella aerogenes is the main histamine producer in patients with IBS
The researchers then went back to analyze the donor stool more closely. IBS patients with high urine histamine had a gut microbiome that produced significantly more histamine. They set out to determine which microbes might be responsible.
In total, they isolated 164 different gut microbes and tested their capacity to produce histamine. The authors reported that:
- In IBS patients with high urine histamine, Klebsiella aerogenes was the main histamine producer. In fact, aerogenes produced 100 times more histamine than any other bacterial isolate!
- In IBS patients and low urine histamine, Enterococcus faecium and Enterococcus faecalis were the primary producers of histamine.
Unfortunately, the paper did not include a complete list of the bacteria tested and their histamine-producing capacity. For instance, previous research has highlighted Morganella morganii as a potential producer of gut histamine,3,4 but there was no mention of this microbe in the results or discussion.
It’s also entirely possible that other histamine producers (perhaps those less easily cultured) may have been missed in the selection of microbes tested.
Nevertheless, K. aerogenes was highly abundant in three different cohorts of IBS patients and was reduced on a low FODMAP diet. Additionally, germ-free mice colonized with K. aerogenes produced 77 times more histamine than those colonized with another species of Klebsiella.
pH matters: Why the acidity of the colon is essential
So how does K. aerogenes produce histamine? It uses an enzyme called histamine decarboxylase, or hdc. The hdc enzyme converts histidine, an essential amino acid found in the diet, into histamine.
Since previous studies had found the activity of this enzyme to be affected by pH, the researchers decided to test to whether histamine production by K. aerogenes was dependent on the acidity of the environment. Indeed, K. aerogenes produced the most histamine at a pH of 7.0 and almost no histamine at a pH below 6.0 or above 8.0.
This is key, as the pH of the colon ranges from 5.5 to 7.5, depending on fermentation levels. A pH at the lower end of this range is typically associated with better health. In other words, reducing the pH of the colon (increasing its acidity) could be one way to reduce gut histamine production by K. aerogenes.
Lactobacilli: a way to keep Klebsiella at bay
Of course, one of the primary determinants of colonic pH is lactic acid levels. When the researchers looked at gut samples from the “humanized” mice, they found that lactic acid levels were much lower in mice that had received a microbiota from IBS patients with high urine histamine. This was accompanied by lower levels of lactic-acid-producing bacteria like lactobacilli.
To further examine this relationship, the researchers cultured K. aerogenes with or without a mixture of lactobacilli. As expected, the lactobacilli decreased histamine production! The lab also confirmed these results in a mouse model.
Unfortunately, the two lactobacilli used in this study are not well-characterized. The first is thought to be a strain of either L. animalis or L. murinus, while the second is more closely related to L. acidophilus and L. lactis.
Nonetheless, this suggests that some lactobacilli can modulate histamine production by K. aerogenes, most likely by producing lactic acid, thereby decreasing the pH and the activity of the hdc enzyme.
Of course, many lactobacilli can be problematic for those with symptoms of histamine intolerance or mast cell activation. But more on that later.
What about Klebsiella in the small intestine?
So far, we’ve been talking about Klebsiella activity in the colon. But what about Klebsiella in the small intestine?
While the small intestine does not normally harbor much Klebsiella, at least one study has shown that Klebsiella species are more prevalent in the duodenum (upper third of the small intestine) of individuals with GI symptoms and that they can disrupt the overall small intestinal microbial community structure.5
Preliminary evidence suggests that some of these Klebsiella species may originate from the oral cavity.5 In other words, saliva may act as a reservoir for continued Klebsiella transmission to the gut, where they will flourish if the gut environment allows.6
Portions of the small intestine are also much less acidic than the colon. Recent reports suggest pH levels as high as pH 7.4-7.8 in the ileum (the most distal part of the small intestine),7 levels that could certainly support histamine production by K. aerogenes.
In other words, an opportunistic overgrowth of K. aerogenes in the small intestine could contribute to overall high levels of histamine.
Bacterial histamine attracts mast cells to the gut
Last but not least, the researchers again turned to mice to determine how bacterial histamine might cause visceral pain.
They found that bacterial histamine signals through the histamine 4 receptor to activate mast cells and attract them to the colon. These mast cells contribute even more histamine and other pain-signaling molecules, triggering nerve cells in the gut and causing abdominal pain.
Blocking H4 receptors may, therefore, represent a strategy to mitigate symptoms in patients with high histamine. This would prevent the recruitment of mast cells to the colon and additional histamine production by the host.
How to test for bacterial histamine-related IBS
So how do you know if you’re in this particular subset of IBS patients? While more studies are needed to precisely define the features of this type of IBS, it is likely that indicators will include:
- High urine histamine levels. This can be measured through a 24-hour urine histamine test, available from Quest, LabCorp, or DirectLabs.
- A high abundance of K. aerogenes on a sequence-based stool test. This can be found in the raw data of the Thorne Gut Health test or similar metagenomics tests. (Note: I’d also look for a high abundance of M. morganii, which other studies have identified as a potentially significant histamine producer.)
- Other symptoms of mast cell activation, “histamine intolerance”, or sensitivity to FODMAPs. If testing is not feasible but you have other symptoms of mast cell activation, you might be more likely to be in this subset of IBS patients.
If you have two or more of these, it might be worth trying some of the strategies I have compiled below.
Strategies to target bacterial histamine-related IBS
Below is a list of potential interventions that may be helpful for those with this particular subset of IBS.
Note: This information should not be taken as medical advice. Always consult with your personal physician about whether a particular intervention is appropriate for you.
- A low FODMAP diet: a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can acutely decrease gut histamine levels, reduce the abundance of K. aerogenes, and offer temporary relief from abdominal pain.
- Restore gut acidity: a lower pH was shown to significantly reduce histamine production by K. aerogenes.
The following are likely most effective for increasing gut acidity, but may not be tolerated by histamine-sensitive individuals; only use if well-tolerated:
- Lactobacilli – most lactobacilli produce some lactic acid and will reduce gut pH. For those who are histamine sensitive, Lactobacillus plantarum 299v has shown benefits in clinical trials for IBS8 and may be better tolerated by those who are sensitive to histamine.9
- Vinegar – vinegar is 5% percent acetic acid and has been shown to decrease colonic pH in an animal model.10
- Lacto-fermented foods – traditionally fermented dairy products and vegetables contain high amounts of lactobacilli, lactic acid, and other organic acids that can reduce gut pH.
Other interventions that are likely to be better tolerated in histamine-sensitive individuals:
- Butyrate – SCFA levels are a key factor in determining colonic pH. Supplementing with butyrate may help to promote acidity and has the added benefit of suppressing mast cell activation.11,12
- Betaine HCl – supplemental HCl may help reduce the pH of the stomach and small intestine around meals when dietary histidine is present.
- Reduce colon transit time – faster transit time has been linked to a more acidic gut pH.13 Both magnesium and vitamin C can accelerate transit time and are also helpful for supporting histamine turnover.
- Reduce gut oxygen: K. aerogenes is a member of the Enterobacteriaceae family and can utilize oxygen. This means that the strategies outlined in my article on the oxygen-dysbiosis connection might be helpful for reducing the abundance of K. aerogenes. The PPAR-gamma activating herbs silymarin and curcumin are also effective mast cell stabilizers.
- Time-restricted eating: K. aerogenes has been shown to have a circadian rhythm and proliferates more rapidly in the presence of melatonin.14 This suggests that aligning meals with the circadian clock (i.e. don’t eat late at night) or even a time-restricted eating window may be helpful.
- Low histamine diet: While we don’t have any studies on a ‘low histamine diet’, I have seen this to be beneficial in my work with clients with IBS and symptoms of mast cell activation. It seems reasonable that reducing dietary sources of histidine, the substrate for the hdc enzyme, would reduce histamine production by K. aerogenes.
- Quercetin: A natural histamine 4 receptor antagonist,15 quercetin may help offset the effects of bacterial histamine on mast cell accumulation in the gut and thus reduce gut hypersensitivity.
Summary and takeaways
I know we covered a lot, so here are the major things to take away from this article:
1)The gut microbiota is a significant source of histamine: “Although, traditionally, mast cells have been considered to be the main source of histamine, our findings point to the gut microbiota as an important source.”
2) Klebsiella aerogenes is a major (if not the) culprit for elevated histamine in patients with IBS. Bacterial histamine from K. aerogenes can recruit and activate mast cells in the gut, leading to abdominal pain. K. aerogenes may also be involved in other conditions characterized by high histamine levels, but more studies are needed.
3) A subset of IBS patients with high histamine may benefit from targeted therapies that reduce K. aerogenes or inhibit histamine signaling: “The identification of K. aerogenes, or bacteria with similar hdc activity, as a source of histamine in the gut may guide dietary recommendations, microbiota-directed therapies, or use of H4 receptor antagonists in a subset of patients with IBS with chronic abdominal pain.” I discussed many such strategies above.
That’s all for now! Let me know if you enjoyed this article and share your thoughts in the comments below.
Interested in more about histamine and IBS? Join my Patreon community and get access to exclusive content, including:
- Mast cells and food-induced abdominal pain
- The dual effects of histamine
- Host DAO in gut inflammation
- Thoughts on the low FODMAP diet
- Diet & lifestyle strategies for histamine intolerance
The gut bacteria that produce histamine in IBS – revealed!
Histamine can be secreted by many bacteria, but the particular microbes responsible for histamine overproduction in the gut have remained a mystery – until now. Read on as I break down the findings from a long-awaited study that uncovers the role of bacterial histamine in irritable bowel syndrome, and the gut bacteria involved!
Histamine is a compound released by immune cells and involved in the local immune response. It is also a known mediator of pain.
In recent years, histamine has become increasingly implicated in irritable bowel syndrome (IBS). It is also thought that the various symptoms characteristic of “histamine intolerance” might be due to an overproduction of histamine in the gut, overwhelming the body’s ability to break down and metabolize histamine.
Now, a new study published in Science Translational Medicine suggests that bacterial histamine can induce abdominal pain in a subset of patients with IBS.1 Moreover, it identifies the bacterium Klebsiella aerogenes as the primary producer of gut histamine!
In this article, I break down these new findings and discuss the implications. First, some quick background to explain the motivation for this latest study.
Low FODMAP diets reduce urine histamine in patients with IBS
Low FODMAP diets have long been recognized for their ability to help mitigate symptoms in patients with IBS. However, the exact mechanism by which these carbohydrates worsen gut symptoms has been unclear.
In 2017, a group of researchers at McMaster University randomly assigned IBS patients to consume a low or high FODMAP diet.2 After the dietary intervention, they measured a variety of metabolites in the urine.
They found that about a third of the IBS patients had high urine histamine levels at baseline, and that urine histamine was 8 times lower after the low FODMAP diet.
Diet – microbiota interactions lead to increased gut sensitivity
Building on these findings in their most recent study, the researchers transplanted the gut microbiota from (1) an IBS patient with high urine histamine, (2) an IBS patient with low urine histamine, and (3) a healthy control subject into three separate groups of germ-free mice.
After a colonization period to allow the microbiotas to take hold in the mice, they further split each group of mice in two, to receive a low or high fermentable carbohydrate diet.
Lo and behold, only the group of mice colonized with the microbiota from the IBS patient with high urine histamine and fed the high fermentable carbohydrate diet had increased gut sensitivity!
Klebsiella aerogenes is the main histamine producer in patients with IBS
The researchers then went back to analyze the donor stool more closely. IBS patients with high urine histamine had a gut microbiome that produced significantly more histamine. They set out to determine which microbes might be responsible.
In total, they isolated 164 different gut microbes and tested their capacity to produce histamine. The authors reported that:
- In IBS patients with high urine histamine, Klebsiella aerogenes was the main histamine producer. In fact, aerogenes produced 100 times more histamine than any other bacterial isolate!
- In IBS patients and low urine histamine, Enterococcus faecium and Enterococcus faecalis were the primary producers of histamine.
Unfortunately, the paper did not include a complete list of the bacteria tested and their histamine-producing capacity. For instance, previous research has highlighted Morganella morganii as a potential producer of gut histamine,3,4 but there was no mention of this microbe in the results or discussion.
It’s also entirely possible that other histamine producers (perhaps those less easily cultured) may have been missed in the selection of microbes tested.
Nevertheless, K. aerogenes was highly abundant in three different cohorts of IBS patients and was reduced on a low FODMAP diet. Additionally, germ-free mice colonized with K. aerogenes produced 77 times more histamine than those colonized with another species of Klebsiella.
pH matters: Why the acidity of the colon is essential
So how does K. aerogenes produce histamine? It uses an enzyme called histamine decarboxylase, or hdc. The hdc enzyme converts histidine, an essential amino acid found in the diet, into histamine.
Since previous studies had found the activity of this enzyme to be affected by pH, the researchers decided to test to whether histamine production by K. aerogenes was dependent on the acidity of the environment. Indeed, K. aerogenes produced the most histamine at a pH of 7.0 and almost no histamine at a pH below 6.0 or above 8.0.
This is key, as the pH of the colon ranges from 5.5 to 7.5, depending on fermentation levels. A pH at the lower end of this range is typically associated with better health. In other words, reducing the pH of the colon (increasing its acidity) could be one way to reduce gut histamine production by K. aerogenes.
Lactobacilli: a way to keep Klebsiella at bay
Of course, one of the primary determinants of colonic pH is lactic acid levels. When the researchers looked at gut samples from the “humanized” mice, they found that lactic acid levels were much lower in mice that had received a microbiota from IBS patients with high urine histamine. This was accompanied by lower levels of lactic-acid-producing bacteria like lactobacilli.
To further examine this relationship, the researchers cultured K. aerogenes with or without a mixture of lactobacilli. As expected, the lactobacilli decreased histamine production! The lab also confirmed these results in a mouse model.
Unfortunately, the two lactobacilli used in this study are not well-characterized. The first is thought to be a strain of either L. animalis or L. murinus, while the second is more closely related to L. acidophilus and L. lactis.
Nonetheless, this suggests that some lactobacilli can modulate histamine production by K. aerogenes, most likely by producing lactic acid, thereby decreasing the pH and the activity of the hdc enzyme.
Of course, many lactobacilli can be problematic for those with symptoms of histamine intolerance or mast cell activation. But more on that later.
What about Klebsiella in the small intestine?
So far, we’ve been talking about Klebsiella activity in the colon. But what about Klebsiella in the small intestine?
While the small intestine does not normally harbor much Klebsiella, at least one study has shown that Klebsiella species are more prevalent in the duodenum (upper third of the small intestine) of individuals with GI symptoms and that they can disrupt the overall small intestinal microbial community structure.5
Preliminary evidence suggests that some of these Klebsiella species may originate from the oral cavity.5 In other words, saliva may act as a reservoir for continued Klebsiella transmission to the gut, where they will flourish if the gut environment allows.6
Portions of the small intestine are also much less acidic than the colon. Recent reports suggest pH levels as high as pH 7.4-7.8 in the ileum (the most distal part of the small intestine),7 levels that could certainly support histamine production by K. aerogenes.
In other words, an opportunistic overgrowth of K. aerogenes in the small intestine could contribute to overall high levels of histamine.
Bacterial histamine attracts mast cells to the gut
Last but not least, the researchers again turned to mice to determine how bacterial histamine might cause visceral pain.
They found that bacterial histamine signals through the histamine 4 receptor to activate mast cells and attract them to the colon. These mast cells contribute even more histamine and other pain-signaling molecules, triggering nerve cells in the gut and causing abdominal pain.
Blocking H4 receptors may, therefore, represent a strategy to mitigate symptoms in patients with high histamine. This would prevent the recruitment of mast cells to the colon and additional histamine production by the host.
How to test for bacterial histamine-related IBS
So how do you know if you’re in this particular subset of IBS patients? While more studies are needed to precisely define the features of this type of IBS, it is likely that indicators will include:
- High urine histamine levels. This can be measured through a 24-hour urine histamine test, available from Quest, LabCorp, or DirectLabs.
- A high abundance of K. aerogenes on a sequence-based stool test. This can be found in the raw data of the Thorne Gut Health test or similar metagenomics tests. (Note: I’d also look for a high abundance of M. morganii, which other studies have identified as a potentially significant histamine producer.)
- Other symptoms of mast cell activation, “histamine intolerance”, or sensitivity to FODMAPs. If testing is not feasible but you have other symptoms of mast cell activation, you might be more likely to be in this subset of IBS patients.
If you have two or more of these, it might be worth trying some of the strategies I have compiled below.
Strategies to target bacterial histamine-related IBS
Below is a list of potential interventions that may be helpful for those with this particular subset of IBS.
Note: This information should not be taken as medical advice. Always consult with your personal physician about whether a particular intervention is appropriate for you.
- A low FODMAP diet: a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can acutely decrease gut histamine levels, reduce the abundance of K. aerogenes, and offer temporary relief from abdominal pain.
- Restore gut acidity: a lower pH was shown to significantly reduce histamine production by K. aerogenes.
The following are likely most effective for increasing gut acidity, but may not be tolerated by histamine-sensitive individuals; only use if well-tolerated:
- Lactobacilli – most lactobacilli produce some lactic acid and will reduce gut pH. For those who are histamine sensitive, Lactobacillus plantarum 299v has shown benefits in clinical trials for IBS8 and may be better tolerated by those who are sensitive to histamine.9
- Vinegar – vinegar is 5% percent acetic acid and has been shown to decrease colonic pH in an animal model.10
- Lacto-fermented foods – traditionally fermented dairy products and vegetables contain high amounts of lactobacilli, lactic acid, and other organic acids that can reduce gut pH.
Other interventions that are likely to be better tolerated in histamine-sensitive individuals:
- Butyrate – SCFA levels are a key factor in determining colonic pH. Supplementing with butyrate may help to promote acidity and has the added benefit of suppressing mast cell activation.11,12
- Betaine HCl – supplemental HCl may help reduce the pH of the stomach and small intestine around meals when dietary histidine is present.
- Reduce colon transit time – faster transit time has been linked to a more acidic gut pH.13 Both magnesium and vitamin C can accelerate transit time and are also helpful for supporting histamine turnover.
- Reduce gut oxygen: K. aerogenes is a member of the Enterobacteriaceae family and can utilize oxygen. This means that the strategies outlined in my article on the oxygen-dysbiosis connection might be helpful for reducing the abundance of K. aerogenes. The PPAR-gamma activating herbs silymarin and curcumin are also effective mast cell stabilizers.
- Time-restricted eating: K. aerogenes has been shown to have a circadian rhythm and proliferates more rapidly in the presence of melatonin.14 This suggests that aligning meals with the circadian clock (i.e. don’t eat late at night) or even a time-restricted eating window may be helpful.
- Low histamine diet: While we don’t have any studies on a ‘low histamine diet’, I have seen this to be beneficial in my work with clients with IBS and symptoms of mast cell activation. It seems reasonable that reducing dietary sources of histidine, the substrate for the hdc enzyme, would reduce histamine production by K. aerogenes.
- Quercetin: A natural histamine 4 receptor antagonist,15 quercetin may help offset the effects of bacterial histamine on mast cell accumulation in the gut and thus reduce gut hypersensitivity.
Summary and takeaways
I know we covered a lot, so here are the major things to take away from this article:
1)The gut microbiota is a significant source of histamine: “Although, traditionally, mast cells have been considered to be the main source of histamine, our findings point to the gut microbiota as an important source.”
2) Klebsiella aerogenes is a major (if not the) culprit for elevated histamine in patients with IBS. Bacterial histamine from K. aerogenes can recruit and activate mast cells in the gut, leading to abdominal pain. K. aerogenes may also be involved in other conditions characterized by high histamine levels, but more studies are needed.
3) A subset of IBS patients with high histamine may benefit from targeted therapies that reduce K. aerogenes or inhibit histamine signaling: “The identification of K. aerogenes, or bacteria with similar hdc activity, as a source of histamine in the gut may guide dietary recommendations, microbiota-directed therapies, or use of H4 receptor antagonists in a subset of patients with IBS with chronic abdominal pain.” I discussed many such strategies above.
That’s all for now! Let me know if you enjoyed this article and share your thoughts in the comments below.
Interested in more about histamine and IBS? Join my Patreon community and get access to exclusive content, including:
- Mast cells and food-induced abdominal pain
- The dual effects of histamine
- Host DAO in gut inflammation
- Thoughts on the low FODMAP diet
- Diet & lifestyle strategies for histamine intolerance
Dear Lucy,
Your blog is truly phenomenal, and I’m not usually a blog reader. I came across it whilst researching whether or not I should take MegaSporebiotic post-antibiotic treatment for “SIBO” (reading your blog raises questions whether it’s actually that or not, but that’s an aside).
I have a question: From reading through many of your articles, my takeaway, for someone like me who has been diagnosed with potential SIBO, taken the antibiotics, and am currently on the SIBO Bi-phasic diet (for 3 months or so – longer seems like maybe not a good idea), and taking prokinetics at night, is that I really shouldn’t bother taking a probiotic, as it may actually delay microbiome regeneration. Am I correct in this interpretation? But then you DO recommend the CoreBiotic, so at what point to you recommend introducing it?
Apart from that, I am taking Butyrate and Glutamine, which you mention several times. Is there anything else I should taking apart from other, physical interventions (exercise, outdoors, etc.)?
It would be fantastic if you could respond, as it would help my journey immensely!
Thanks for all your work.
I have been having histamine intolerance for more than a decade now, with several mental and physical symptoms, so my life quaIity was quite reduced. I tried so many things and always assumed a connection with the gut and the bacteria. A stool test showed a reduced acidity and some bacterial disbalance. I think I had a lower amount of lactobacillus.
For a week I‘m now on an only animal based diet, meat and dairy, and I didn’t felt that good for a very long time. Suddenly I can tolerate cheese without any issues.
Now reading your post about the histamine producing bacteria it makes kind of sense. By removing almost all carbohydrates – only a bit of lactose is left – these bacteria don‘t get the food they need to produce histamine, and suddenly I don‘t have a histamine overload anymore and can tolerate histamine in the food.
Can histamine producers survive solely on dietary histidine? What’s the relationship between survival of a microbe like K. Aerogenes, FODMAPs, and histidine? Thank you!
Do you read these studies closely?
The histamine study was done on mice. And histamine has only been shown within the past couple of years to play a role in IBS when it is produced locally by bacteria in the colon. It is not related to food intake of histamine.
“Importantly, bacterial histamine was a chemoattractant for colonic mast cells; mice colonized with high histamine producing IBS faecal microbiota had increased mast cells in the colon in close proximity to enteric neurons.”
https://www.nature.com/articles/s41575-022-00681-z
Also, SIBO has now been shown to be rare (<4% in IBS and non-IBS), unrelated to IBS and the breath tests (lactulose and glucose) have been shown to be unreliable with high false positive. Dr. Pimentel who made the claims about SIBO having a high rate of occurrence IBS made the classic mistake of publishing a popular book before his methods where check by his peers. It took over a decade of expensive research to show his claims were invalid.
"The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial composition of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-associated bacterial composition, there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS."
https://www.nature.com/articles/s41598-020-57468-y.pdf
Hi Lucy, this article made me fall out of my chair! I have SIBO with extreme histamine intolerance that I can only control so much with diet and DAO – I feel really awful many days with system wide symptoms as histamine will do. I have 76 times as much enterococcus faecalis (yes 76 times) as normal and your article points to the research that shows it is in the top two of histamine producers. I think I found what we need to target to help reduce the histamine thanks to you. Thank you for writing and making it so easy to understand. Do you know how I can get a full copy of the report so I can read further details about the enterococcus faecalis? Sandy
Sandy,
Lucy’s article included this link to the original journal article:
https://www.science.org/doi/10.1126/scitranslmed.abj1895
From there, you will see the abstract (the short summary) of the study for free.
If you want to read the full journal article, click on the red button that says “CHECK ACCESS”. Typically, journal articles can be accessed for free if you’re using a library’s computer or a university or hospital’s computer (those institutions typically have paid journal subscriptions and journal sites will automatically let you access their articles if you’re on the library, hospital, or university’s network). If you’re not accessing a journal over one of those networks, then you’d likely to have to pay for access to read or download the complete article. In this case, the charge I see is $30.00 for this article (fairly typical, though $35 and $40 charges are probably more common for journal articles I come across).
There are probably other work arounds for accessing full scholarly journal articles for free but I have yet to learn them. For example, perhaps there’s a remote login option where you could be at home, visit a library’s website where you’re a member, and from there navigate to the journal article above (this is probably possible with some libraries but I don’t yet know how to do it).
I hope that info is helpful, and more importantly, i hope that you find relief in your suffering.
All the best,
John
Any suggestions on how to incorporate vinegar for this purpose? Is it as simple as adding it to a salad dressing or is there a more effective way?
Thank you so much for all of your hard work, Dr. Mailing! I discovered your work at just the right time, when I felt like there was no guidance I trusted for my ongoing GI issues. Hope you and baby are doing well!
Hi Lucy. Thanks for publishing your research in a way that is understandable for everyone. I would like to donate and support your work, but I find that Patreon is not the way that I want to engage in. It has to do with the personal information they collect and having my credit card at their disposal for monthly charges, this is a matter of protecting personal and financial information. I do enjoy your articles and find them educational. Thank you very much.
Hi Mark! Thanks so much for reading and for wanting to support my work! You can make a one-time donation securely through Stripe on this page: https://www.lucymailing.com/support-me Let me know if that doesn’t suit your preferences.
I find this interesting high PH causes them to produce histamine. Histamine stimulates stomach acid production. It is like they have a built in system to protect the PH of their environment. Some lactobacillus produce a type of histamine that actually tells the body to reduce production of histamines when it attaches to the histamine receptors.
An interesting thought, Lee! Though I’m not sure that bacterial histamine produced in the small or large intestine would impact stomach acid production.
And yes, there are dual effects of histamine! Are you possibly referring to this study? https://journals.asm.org/doi/full/10.1128/mBio.01358-15
This one shows that some strains of L. reuteri can signal through the H2 receptor to suppress inflammation.
Hi Lucy, thanks for this great article, excited to read your new blog posts again! Does histamine overproduction in the gut only cause symptoms of pain, or also other symptoms like gas and bloating? What constellation of symptoms indicate histamine overproduction and mast cell activation in the gut? I have some symptoms of histamine reactions of itchy bumps around my stomach or legs sometimes, but wasn’t sure if that would be indicated from the gut overproduction of histamine.
Can someone have both histamine overproduction, mast cell activation, and H2S? If so, it seems that some of the suggestions for histamine overproduction are contraindicated for H2S (e.g. L plantarum)
Hi RB! Histamine overproduction in the gut has only been causally tied to abdominal pain thus far, but bloating is the #1 most common symptom among people with histamine intolerance: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667364/
However, K. aerogenes is a prolific hydrogen producer. So it’s not clear if the histamine itself causes bloating and distention, or whether it just also produces a lot of hydrogen gas.
While we don’t yet have the research to confirm it, I believe many histamine related symptoms outside of the gut are related to gut overproduction of histamine.
And yes, you can have histamine overproduction / mast cell activation and H2S, in which case the 299v strain might not be the best choice!
Thanks Lucy, this is really helpful! In terms of diagnosing Histamine Intolerance or Overproduction, would you recommend the blood test for serum trypase to detect mast cells and/or whole blood histamine? It seems that serum DAO that they used in the study that you referenced to is not a test that most labs like labcorp or quest offer. I’m curious besides symptoms of histamine overproduction, how a person would confirm if they have this condition as K. aerogenes doesn’t look like it’s tested for on the GI Effects and many other stool tests you recommend as well. Thank you!
Lucy – I am living proof histamine related symptoms outside of the gut exist. My symptoms are body wide (fluish, acne, body aches, pains, congestion, head pressure) and when I eat zero histamine and low FODMAP it improves greatly. If I eat too many carbs (food source for bacteria) or eat histamine (fills my histamine bucket) the symptoms come on full blown for a few days – always starting the morning after. Yes we desperately need more research in this area!
In low-histamine diets, vinegar and citrus are often included in the lists of foods to avoid (alongside others which are acidic). Do you think, then, that this is just mistaken?
Great question! I don’t think this is mistaken. Those foods may still trigger host mast cell activation, leading to unpleasant symptoms. I think the ideal approach is to start to reacidify the gut using the other approaches I suggested, and then as you bring gut bacterial histamine down, you can slowly incorporate more vinegar, citrus, etc as tolerated.
Coincidentally this aligns with my personal experience healing from histamine-related symptoms several years back. I used betaine HCl for months on a lower fermentable diet and only had small amounts of citrus and kombucha until I was able to tolerate more vinegar, Lactobacilli, and lacto-ferments.
That said, it might be ideal to use your “histamine bucket” to emphasize small amounts of acidifying components, while still staying below the threshold that flares symptoms (e.g. favor including small amounts of vinegar over something like chocolate or spinach). Hope that makes sense!
Interesting…. I have suffered with IC for ten years and finally got the connection between Histamine foods and my IC ongoing pain. Since high dosing with turmeric meriva, and lowering my gut PH, my symptoms have disappeared and my gut function is so much better. So hard to get this info so thanks for starting to share the light on what appears to be so complex!
So interesting, thanks for sharing your experience, Jan! Glad you were able to have such dramatic improvement!
Interesting blog, Lucy. I’m just wondering whether there is a strategy for upstream removal/reduction of the ORAL K. aerogenes in order to prevent it from reaching the SI or colon?
Interesting thought, Joanne! I wasn’t able to find much on this, though it appears that periodontitis is a key driver for the expansion of Klebsiella and other Enterobacteriaceae in the oral cavity:
https://www.sciencedirect.com/science/article/pii/S0092867420306814
They suggest for transmigration to the gut you need (1) colonization resistance in the gut to be disrupted and (2) oral inflammation. So supporting good oral health is key!
I’ll likely do a Patreon post on this soon :)
Great article. Thanks for sharing this information, much appreciated.
Thanks for reading, Jay!
Very interesting and great break down, thanks Lucy! I’m going to go check my test results to see if that strain is elevated.
Glad you enjoyed it. Hope you’re able to find it in your results!
Hey Lucy, very informative, thanks a lot for your article.
Based on these new data, would you still recommend AOR Probiotic-3? As it contains Enterococcus faecium.
Good question. A lot of spore probiotics have that strain.
@Kevin thanks for reading! Yes, it’s possible that histamine-sensitive people might react to the AOR product, but it’s still unclear from these data whether all strains of E. faecium and E. faecalis produce histamine. I don’t often recommend AOR just because it has so many additives and there are other soil-based probiotics with more evidence.
Hey Lucy, I missed your answer, but it’s not too late to thank you! have a great day