MTHFR and probiotics

MTHFR and probiotics

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder

Updated On:

February 03, 2026
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How to Select a Probiotic

More information here:

How does MTHFR influence digestion?

While the MTHFR genetic mutation does not directly influence digestion, methylation issues and elevated homocysteine levels associated with MTHFR mutations have been linked to increased inflammation, which may compromise gut barrier integrity and the balance of healthy bacteria.1


Some research has examined potential links between MTHFR mutations and inflammatory bowel disease (IBD), but findings are mixed. Elevated homocysteine, which can result from impaired folate metabolism, may contribute to inflammation in such conditions.2

Other research has linked folate deficiency (which is common in MTHFR) to imbalances in the gut microbiota (dysbiosis). This can also affect healthy digestion.3


A recent study showing a clear link between low folate and altered gut microbiota found that supplementation with probiotics helped to reverse folate deficiency and improve gut microbiota more effectively than synthetic folic acid. The study used a highly efficient folate-producing probiotic strain (called Lactobacillus plantarum GSLP-7 V) which not only restored folate levels and normalized homocysteine but also rebalanced gut microbiota, improving microbial diversity and correcting dysbiosis.4
Also, a balanced gut microbiome can help reduce harmful byproducts from gut bacteria and support methylation pathways. In addition, probiotics may help modulate systemic inflammation, thereby reducing the overall burden on detoxification processes.


Emerging evidence also highlights serotonin dynamics in the gut as an important factor in digestive function and microbiome health. Serotonin (5-HT), which is primarily produced in the gut, plays a central role in regulating gut motility, secretion, visceral sensitivity and low-grade inflammation in conditions such as IBS. Changes in serotonin transporter expression and serotonin availability can influence bowel patterns (e.g., constipation- vs. diarrhea-predominant symptoms) and impact microbial interactions in the intestinal lumen.
Because the gut microbiota helps regulate serotonin levels and signaling, maintaining or improving microbiome balance with probiotics may support healthy serotonin modulation, which in turn supports gut motility and regulates enteric nervous system (ENS).5

MTHFR and digestion: treatment option for digestive issues

If you have a MTHFR genetic mutation and you are also experiencing digestive issues, it’s important to first examine all possible causes of these symptoms. Gastrointestinal issues can have many different causes, including diet, lifestyle, genetics, nutritional deficiencies, environment and other factors.6 It’s a good idea to talk to a healthcare professional or a naturopath.


In addition to supporting digestive function, probiotics may also help with improving folate levels.
Folate from food sources is almost completely absorbed in the small intestine (mostly in the middle section) and does not reach the large intestine. However, certain species of probiotic bacteria are able to synthesize folate, potentially providing an additional source of folate to the gut.7 There is limited evidence suggesting potential vitamin B12 synthesis, though its role in improving B12 levels remains uncertain.8
One study found that supplementation for 12 weeks with Bifidobacterium and Lactobacillus species helped to reduce oxidative stress and inflammation as well as reduce homocysteine levels - which may be helpful for those with MTHFR and high homocysteine.9


Probiotics may be a viable treatment for those affected by depressive symptoms. Research suggests that probiotics may improve mood via the microbiota-gut-brain axis (MGBA), and may be an adjunct treatment for patients with mild depression.10 A 2024 review reported that most studies published between 2014-2023 on probiotic supplementation for depression and anxiety showed beneficial effects.11 However, further research is pending.

Things to be aware of before taking a probiotic if you have MTHFR

While some species of probiotic bacteria can synthesize folate, probiotics should not be considered a substitute for supplementation with active folate (methylfolate). If you have a MTHFR genetic mutation, it is highly recommended that you take methylfolate to directly support normal methylation.

How to choose a probiotic if you have MTHFR

When choosing a probiotic, look for a multi-strain formula with a high CFU count.

MTHFR and probiotics

Key takeaways

  • Icon While MTHFR mutations don’t directly impair the mechanical process of digestion, they may affect nutrient metabolism, gut inflammation and microbial balance.
  • Icon Probiotics help with digestion, nutrient absorption and may support folate levels.
  • Icon Probiotics can help support overall health in people with MTHFR genetic mutations.

Product Recommendations

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Chewable Digestive Enzymes

$46.00

  • Ease Your Belly from Post Meal Discomfort
  • Assists Breakdown of Proteins, Carbohydrates, Lipids, Gluten & Dairy
  • Tastes like a natural, after-dinner mint
  • 3rd-Party Tested, Non-GMO, Gluten-Free, 90 Vegan Tablets

Frequently Asked Questions about MTHFR and probiotics

Do probiotics help MTHFR?

Probiotics may be helpful for those with MTHFR who have digestive issues due to dysbiosis or leaky gut. Probiotic supplementation may also be helpful for those with low folate, as some species can synthesize folate.
In general, probiotics help with increasing the production of digestive enzymes and with the absorption of nutrients, as well as improving the intestinal integrity, enhancing the immune response, increasing the abundance of healthy bacteria in the gut and reducing ‘harmful’ bacteria.

What supplements should be avoided with MTHFR?

Those with the MTHFR genetic mutation should avoid folic acid, as this is the synthetic form of folate and cannot be processed by those who lack the MTHFR enzyme.
If you have other health concerns or you are taking certain medications, it’s important to discuss any supplements with your health professional.

Can MTHFR cause gut issues?

The MTHFR genetic mutation has been linked to some gastrointestinal conditions, including inflammatory bowel disease and increased intestinal permeability (leaky gut syndrome). However, these disorders are more closely related to high homocysteine and inflammation than the MTHFR mutation itself, so not everyone with MTHFR will have gut issues.

The microbiota-gut-brain axis is central to many gut disorders, and research suggests that neurotransmitters such as serotonin, dopamine and GABA can influence gut motility, visceral sensitivity and microbial balance. Low folate may be linked to impaired neurotransmitter synthesis, which may then affect digestive function.12

References

  1. Shanshan Liang, Sixiu Liu, Hua Liu, Xin He, Lingshuang Sun, Lei Chen, Meng Wei, Fanfan Gao, Hongli Jiang; "Homocysteine Aggravates Intestinal Epithelial Barrier Dysfunction in Rats with Experimental Uremia"; Kidney & blood pressure research; 2018

    https://pubmed.ncbi.nlm.nih.gov/30336454/

  2. N Mahmud 1, A Molloy, J McPartlin, R Corbally, A S Whitehead, J M Scott, D G Weir; "Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications"; Gut; 1999

    https://pubmed.ncbi.nlm.nih.gov/10446107

  3. Jian Zhang, Dongyan Cai, Ming Yang, Yijiang Hao, Yuanhua Zhu, Zexuan Chen, Tariq Aziz, Abid Sarwar, Zhennai Yang; "Screening of folate-producing lactic acid bacteria and modulatory effects of folate-biofortified yogurt on gut dysbacteriosis of folate-deficient rats"; Food & function; 2020 Jul

    https://pubmed.ncbi.nlm.nih.gov/32602881/

  4. Jian Zhang, Dongyan Cai, Ming Yang, Yijiang Hao, Yuanhua Zhu, Zexuan Chen, Tariq Aziz, Abid Sarwara, Zhennai Yang; "Screening of folate-producing lactic acid bacteria and modulatory effects of folate-biofortified yogurt on gut dysbacteriosis of folate-deficient rats"; Food & Function; 2020

    https://pubs.rsc.org/en/content/articlelanding/2020/fo/d0fo00480d

  5. Ilmaben S Vahora, Nicholas Tsouklidis, Rajat Kumar, Ravi Soni, Safeera Khan; "How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome"; Cureus; 2020 Aug

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7505258/

  6. Fermin Mearin, Peter Malfertheiner; "Functional Gastrointestinal Disorders: Complex Treatments for Complex Pathophysiological Mechanisms"; Digestive diseases; 2018 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC6067652

  7. G Paolo Strozzi, Luca Mogna; "Quantification of folic acid in human feces after administration of Bifidobacterium probiotic strains"; ournal of clinical gastroenterology; 2008 Sep

    https://pubmed.ncbi.nlm.nih.gov/18685499/

  8. Maddalena Rossi, Alberto Amaretti, Stefano Raimondi; "Folate Production by Probiotic Bacteria"; Nutrients; 2011 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3257725/

  9. Karolina Majewska, Matylda Kręgielska-Narożna, Hieronim Jakubowski, Monika Szulińska, Paweł Bogdański; "The Multispecies Probiotic Effectively Reduces Homocysteine Concentration in Obese Women: A Randomized Double-Blind Placebo-Controlled Study"; Journal of clinical medicine; 2020 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7230928/

  10. Dinyadarshini Johnson, Vengadesh Letchumanan, Chern Choong Thum, Sivakumar Thurairajasingam, Learn-Han Lee; "A Microbial-Based Approach to Mental Health: The Potential of Probiotics in the Treatment of Depression"; Nutrients; 2023 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10053794/

  11. Ermis Merkouris, Theodora Mavroudi, Daniil Miliotas, Dimitrios Tsiptsios, Aspasia Serdari, Foteini Christidi, Triantafyllos K Doskas, Christoph Mueller, Konstantinos Tsamakis; "Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials"; Microorganisms; 2024 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10893170/

  12. Minjia Chen, Guangcong Ruan, Lu Chen, Senhong Ying, Guanhu Li, Fenghua Xu, Zhifeng Xiao, Yuting Tian, Linling Lv, Yi Ping, Yi Cheng, Yanling Wei; "Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome"; Frontiers in endocrinology; 2022 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8888441/

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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