Have Brain Fog & Depression? Leaky Gut Could Be to Blame.

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Have Brain Fog & Depression? Leaky Gut Could Be to Blame.

Numerous studies show link between leaky gut & cognitive issues.

Leaky gut syndrome—also known as increased intestinal permeability—is a state in which the intestinal lining becomes damaged. This allows toxins, bacteria, and foreign particles to leak into the bloodstream. Robust research shows links between leaky gut (and other gut issues) and brain-based issues like cognition and mood. For example, intestinal infection was associated with later onset of anxiety. In other research, elevated zonulin (a marker of leaky gut) was correlated with higher psychological distress and social impairment. Evidence also shows that probiotics and gut-supporting nutrients can help heal these issues. Learn more about what steps to take below.

Dr. Michael Ruscio, DC: Leaky gut could be causing your depression, brain fog, and anxiety. Fortunately, there are some simple treatments like probiotics and gut-supporting nutrients that can help fix the source of this problem. This is Dr. Ruscio, and let’s discuss.

Hi everyone, let’s talk about the connection between your gut and your brain health. This is admittedly a video I’ve been putting off doing for a while, because there is so much evidence documenting this connection that it’s a lot to get through. Let’s jump in, and we’ll go through the evidence in the following order. First we’ll establish that there’s an association between leaky gut, or problems with your gut health, and depression, anxiety, and brain fog. Then we’ll connect this to a mechanism. And we’ll finally show you what therapies are available to help you improve your gut health, so you can improve the cause of things like depression, brain fog, and anxiety.

[Continue reading below]

Dr. R’s Fast Facts Summary

Gut issues are associated with depression, anxiety, and brain fog Gut issues are associated with depression, anxiety, and brain fog

  • IBS patients have more brain-based symptoms like fatigue, poor bodily stamina, sense of coherence, depression and anxiety according to this study.
  • According to this study intestinal infection has an increased likelihood of later developing anxiety
  • Untreated patients with celiac disease experience cognitive impairments or brain fog

The Effects of Leaky Gut

What therapies are available

  • In combination with diet, lowering stress, and exercise, probiotics can be a great tool for gut improvement.
  • Try the probiotic protocol in Healthy Gut, Healthy You
  • There are several studies, meta-analysis, and randomized controlled trials that support probiotic use. Probiotics lead to improved depression, anger, anxiety and lower cortisol

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Leaky Gut Linked to Cognitive, Mood Issues

So, to start, this study: “Major depression model induced by repeat and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and neuroprogressive alterations.” Essentially—I’ll just summarize for you here—in this experimental study, they couldn’t do this in humans because it would be cruel to inflict harm and also unethical to inflict harm to humans. (But unfortunately we can do this in mice.) What was done in this study essentially was, LPS—or lipopolysaccharide, which is a fragment of bacterial cell walls—was injected into these mice. A correlation was shown between LPS levels and depression. I’ll come down here to the conclusion:

In conclusion, our results support the validity of the chronic LPS [lipopolysaccharide] model of major depression and additionally shows its translational relevance with respect to neuroimmune and neuroprogressive pathways.

Essentially what they’re showing here is that when we inject mice with LPS, they have negative changes in their brain. LPS will become higher in humans when you have a leaky gut. This is showing that if we essentially facilitated the same mechanism of leaky gut in mice, those mice have degenerative changes in their brain health.

Now, that’s mice. I show you that just to show you the mechanism. But let’s see what happens in more of a real-world setting. Next study is “Fatigue: a distressing symptom for patients with irritable bowel syndrome.” So those with irritable bowel syndrome—gas, bloating, constipation, diarrhea, loose stools—will ostensibly have leaky gut. Or at least they have an increased prevalence of leaky gut. In this study, a total of 160 patients with IBS completed a questionnaire, and the conclusions from these researchers:

Fatigue is a distressing symptom which occurs in a sizeable proportion of patients with IBS. It affects life in a multidimensional way, with poor bodily stamina being the most prominent feature. Fatigue, along with sense of coherence, [or another way of saying brain fog] depression and anxiety needs to be assessed, confirmed and targeted for interventions.

So we’re seeing IBS patients have more of these brain-based symptoms.

Another study: “Intestinal infection associated with future onset of anxiety disorder: Results of a nationally representative study.” This study essentially looked at what happened to people’s anxiety over time. I’ll come down here to paraphrase them. Overall, intestinal infection increased likelihood of later development of anxiety. So even more evidence.

Further yet still, another study, “Gluten-induced cognitive impairment (‘brain fog’) in celiac disease.” Essentially, skipping down to their conclusion,

Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten-free diet.”

Now, that is in a model of those with celiac. We can’t necessarily extrapolate that to say everyone needs to follow a gluten-free diet, but it’s certainly something to consider.

Now, we’ve looked at the association between problems in the gut and brain fog. And we hinted at the leaky gut mechanism before. Let’s go over one or two more evidence points substantiating that leaky gut is the underlying cause of these brain-based symptoms. “Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?” Their conclusion:

Older adults with GI symptoms express increased plasma levels of zonulin [a marker of leaky gut], which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes.

We’re seeing fairly compelling evidence here that, in those with more psychological distress, there is a higher distribution of leaky gut in that population.

Okay, moving on. Another study: “Increased zonulin is associated with hyperactivity and social dysfunction in children with attention deficit hyperactivity disorder.” Essentially, coming down to the conclusion here,

In this sample of children with ADHD, elevated zonulin levels were associated with increased symptoms of hyperactivity and impairment of social functioning.

So in children and in adults, we see this association. We see researchers able to replicate this in the lab with mice, and we see that those with IBS have a higher predilection toward these brain-based symptoms. There’s a fairly clear case here that if there’s something wrong in the gut, it’s going to connect to your brain. This is the gut-brain connection.

Compelling Evidence Shows Probiotics Help

Now, what do we do? How can we take this understanding that problems in the gut can manifest as anxiety, depression, and brain fog, and then treat that? Well, fortunately, we have some evidence here showing that probiotics and gut-supportive nutrients can help. This first study here looked at the effect of probiotics. They found probiotics led to improved depression, anger, anxiety, and also lowered the stress hormone cortisol. That is pretty compelling.

Another study here, “Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” This is arguably our highest level of scientific evidence. To quote,

We found that probiotics were associated with a significant reduction in depression, underscoring the need for additional research on this potential preventative strategy for depression.”

Another meta-analysis of 10 clinical trials looking at over 1300 patients. And I want to paint one important nuance here, so let me quote, “There was no significant difference in mood between the treatment and placebo groups post-intervention.” After the intervention in the treatment and placebo group, there was no difference. This is important, because if there are people who are looking to be contrarian and say probiotics are complete BS, this is likely what they will study. But that would be a misrepresentation of the data, because if you read further you see,

A separate subgroup analysis of the studies conducted in healthy versus depressed individuals found significant improvements in the moods of individuals with mild to moderate depressive symptoms.”

What this is telling you is that if your mood is fine, you don’t seem to get any happier or see any additional improvement above a normal level. But if your mood is depressed, that’s when the probiotics seem to have benefit. This would make sense. It’s like saying that if we used a weight loss intervention in people who are at a normal weight, it doesn’t show effectiveness. That would make sense: these people don’t need to lose any weight. But if we apply that same intervention to a group of overweight people, then we can see effect. That’s kind of the concept there.

Now, another report here, a systematic review. To quote,

The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and the duration of treatment varied widely…

Now that, in my mind, is actually a good thing. Researchers don’t like this because researchers like to be able to say, “Well, this is the one strain of probiotic, it has to be used for this long, and this is the exact protocol you should follow.” My feeling is that probiotics are not like drugs. They don’t need to have a certain dose or certain duration. They’re more of a global support for your gut. They can positively impact your gut milieu. And I do not think that the strain is highly important, but rather I like patients to use the three probiotics that we’ve developed in our three category system, so that you can personalize the probiotic protocol to your gut.

I’ll put a screenshot up here on the screen. Here are the three probiotic categories that I recommend: a Lactobacillus-Bifidobacterium blend, a Saccharomyces boulardii, and a soil-based probiotic. If you look at all the probiotic research, you can organize every formula that’s been used (for the most part) into one of these three categories. They’ve all shown benefit.

Now, not everyone will react well to every category of probiotic. You can try all three at once, or if you’re really sensitive and reactive, try one at a time. Keep using whatever formula feels good to your gut. If all three feel good, great. Now instead of using just one probiotic, you’re using three to give your body this nice broad probiotic stimulus. If for some reason you have a negative reaction, which happens sometimes—it’s rare but it does happen—then you can discontinue whatever probiotics seem to not sit well with your system, and then use the other one or two formulas.

Sponsored Resources


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Moving on. Another trial here. And this is very compelling, a randomized controlled trial, with a placebo-controlled arm, of course, found that probiotic administration in patients with major depressive disorder for eight weeks had a beneficial effect on the Beck Depression Inventory (essentially a questionnaire to assess depression).

Then finally, another randomized controlled trial finding that probiotics tend to make people happier. So, some pretty compelling evidence there for probiotics.

Now, I want to also be careful to say that probiotics are not a panacea. They’re not a cure-all. And you will see, unfortunately, nefarious marketing claims on the internet regarding probiotics. I understand why some have urged caution regarding probiotics. For example, you will see some probiotics marketed as a weight-loss probiotic. There is documentation that probiotics can lead to weight loss, but the effect is very small. That would be a misleading claim to say, “Well, a research study found that probiotics can help with weight loss.” True, but when you’re looking at about two to three pounds in obese subjects, that’s not really anything to write home about. It was mathematically significant, but it wasn’t what I would call clinically meaningful.

Gut-Supporting Nutrients, Lifestyle Can Also Heal

The other treatment here that I want to point out to you is gut-supportive nutrients. This final study is: “Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria.” So they assessed that serum concentration of LPS (the lipopolysaccharide that we discussed before) in a group of patients and they essentially looked at the LPS, a measure of leaky gut, before and after giving this nutrient cocktail that’s supposed to support the gut (including glutamine, N-acetyl cysteine, and zinc). They found there was a reduction in these markers after administration of this gut-supporting cocktail. So again, in summary, patients with leaky gut use a nutrient-supporting cocktail for a number of weeks. When the leaky gut markers are retested, the leaky gut improves. So this is another therapy to consider adding in.

Now, this always should be done in conjunction, at the very least, with a healthy diet and lifestyle. So sleep, stress, exercise should all be attended to. And healthy diet is a relative term: you could use a paleo-like diet, a Mediterranean-like diet, a vegetarian-like diet if that’s your preference, as long as you’re focusing on whole, unprocessed, unadulterated food. Depending on what’s going on in your gut you may need to personalize that. If you need a resource, I do give quite detailed recommendations for how to figure out what diet is best for your gut in Healthy Gut, Healthy You.

Have Brain Fog & Depression? Leaky Gut Could Be to Blame. - 3d MC L

If you’re struggling with depression, anxiety, and brain fog, remember that your gut could very likely be the cause. It’s not a guarantee, but it’s fairly likely, especially if you have digestive symptoms. Probiotics and gut-supportive nutrition can help with repairing your gut, thus remedying the cause of the anxiety, brain fog, and depression.

This is Dr. Ruscio, and I hope you find this helpful. And I really hope you act, because as someone who’s suffered with brain fog, I know how debilitating and unpleasant it can be. Don’t go another day not feeling cognitively normal. Take these simple steps to improve your gut health and improve your brain health, and then be able to be happier, more engaged, and sharper in your day-to-day life. Again, I hope this was helpful, and we will talk to you next time.

➕ Links & References
  • Rodrigues FTS, de Souza MRM, Lima CNC, da Silva FER, Costa DVDS, Dos Santos CC, Miyajima F, de Sousa FCF, Vasconcelos SMM, Barichello T, Quevedo J, Maes M, de Lucena DF, Macedo D. Major depression model induced by repeated and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and neuroprogressive alterations. J Psychiatr Res. 2018 Dec;107:57-67. doi: 10.1016/j.jpsychires.2018.10.003. Epub 2018 Oct 5. PMID: 30326340.
  • Frändemark Å, Jakobsson Ung E, Törnblom H, Simrén M, Jakobsson S. Fatigue: a distressing symptom for patients with irritable bowel syndrome. Neurogastroenterol Motil. 2017 Jan;29(1). doi: 10.1111/nmo.12898. Epub 2016 Jul 11. PMID: 27401139.
  • Bruch JD. Intestinal infection associated with future onset of an anxiety disorder: Results of a nationally representative study. Brain Behav Immun. 2016 Oct;57:222-226. doi: 10.1016/j.bbi.2016.05.014. Epub 2016 May 17. PMID: 27223096.
  • Yelland GW. Gluten-induced cognitive impairment (“brain fog”) in coeliac disease. J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:90-93. doi: 10.1111/jgh.13706. PMID: 28244662.
  • Ganda Mall JP, Östlund-Lagerström L, Lindqvist CM, Algilani S, Rasoal D, Repsilber D, Brummer RJ, Keita ÅV, Schoultz I. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress? BMC Geriatr. 2018 Mar 20;18(1):75. doi: 10.1186/s12877-018-0767-6. PMID: 29554871; PMCID: PMC5859527.
  • Özyurt G, Öztürk Y, Appak YÇ, Arslan FD, Baran M, Karakoyun İ, Tufan AE, Pekcanlar AA. Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder. Compr Psychiatry. 2018 Nov;87:138-142. doi: 10.1016/j.comppsych.2018.10.006. Epub 2018 Oct 29. PMID: 30414552.
  • Huang R, Wang K, Hu J. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016 Aug 6;8(8):483. doi: 10.3390/nu8080483. PMID: 27509521; PMCID: PMC4997396.
  • Ng QX, Peters C, Ho CYX, Lim DY, Yeo WS. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J Affect Disord. 2018 Mar 1;228:13-19. doi: 10.1016/j.jad.2017.11.063. Epub 2017 Nov 16. PMID: 29197739.
  • Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017 Feb 20;16:14. doi: 10.1186/s12991-017-0138-2. Erratum in: Ann Gen Psychiatry. 2017 Mar 7;16:18. PMID: 28239408; PMCID: PMC5319175.
  • Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition. 2016 Mar;32(3):315-20. doi: 10.1016/j.nut.2015.09.003. Epub 2015 Sep 28. PMID: 26706022.
  • Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 Aug;48:258-64. doi: 10.1016/j.bbi.2015.04.003. Epub 2015 Apr 7. PMID: 25862297.
  • Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10. PMID: 19112401.
  • Lactobacillus-Bifidobacterium blend
  • Saccharomyces boulardii
  • Soil-based probiotic
  • Dr. Ruscio’s Additional Resources

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