Depression, The Microbiome & Leaky Gut

One of the things I explore in depth in Brain Maker is the notion that even depression is now considered an inflammatory disorder. We now understand that inflammatory markers, the same that we see elevated in heart disease are also elevated in the depressed patient. So the question is: If depression is an inflammatory disorder then where does the inflammation come from? Interestingly that is more or less the title of a study that was recently published in a British medical journal in 2013. In this video we take a closer look at the gut microbiome, leaky gut and how it relates to disorders such as depression.

  • costermonger

    Depression – my understanding is that there are two separate types of depression – reactive and inherited. How does inherited depression tie in with leaky gut? I don’t see the connection.

    • TeamDoctorsClinic

      Do you think they are either one or the other? Inherited depression is ONLY effected by the gene and not the environment? Someone “feels” a certain way or their mood is such and since it is inherited you just say “its inherited so there is nothing we can do for you?” bye Come on…

    • Lynn Dell

      It’s the same working principle behind telling people who have 2 x apoe4 that that need not lead to Alzheimer’s, or since one has lp(a) genetic predisposition (although we don’t know for sure, Dr. Davis bet I have that issue) that one can’t do anything to minimize its effects.

      The key term is “epigenetic modulation” and the key ways we alter gene expression are diet and exercise, sleep, and proper hydration.

      In other words, you can lessen the impact of what might be a genetic predisposition by what you eat, how you exercise, how you sleep, etc.. This information is so exciting and gives me a lot of hope after many years of discouragement. We have it in our power to bring out the best in the DNA we have been given, and probiotic nourishment is a HUGE player in this arena.

  • catwoman

    Dr. Perlmutter, would foods that cause inflammation in humans also have the same affect on dogs?

    • TechnoTriticale

      re: … same effect on dogs?

      You need to assume so. It’s likely a subset of the larger problem that today’s carnivore pet foods are largely junk. The majority contain grains, often gluten-bearing grains, and they are too high in carbs generally. This does the same damage to dogs and cats as it does to people. Diabetes in pets used to be unheard of. It’s now common.

  • Rachel

    My son has ALS–If he had elevated LPS levels in his gut….what will help this condition????

    • TeamDoctorsClinic

      The only way to find out is to try it. You have nothing to lose by improving your sons diet, do you?

    • David Perlmutter

      This is clearly going to be an area of intense research (I hope). Overall, we target gut permeability in our ALS patients

  • Diane

    Hi Dr Perlmutter,
    Will Brain Maker explore ways to avoid the development (and treatment) of leaky gut issues?

    • David Perlmutter


      • Diane

        Great! Looking forward to reading it!

  • Lynn Dell

    I have the book on pre-order, and am looking forward to it!

    As one of the “walking wounded,” I took antibiotics for quite some months during my senior year in college, then when I started working in 1980, the stress of moving away from family, starting a new job, and a couple other life stress issues about put me under. Although I was still functioning, when alone I was crying practically all the time, and I would go to bed, and was almost totally not able to sleep. In the morning, I would want to sleep, but could not. There was a perfect storm going on at the time – and now I see I need to add antibiotics to that storm’s list of factors.

    If it’s a situational kind of depression, the gut reaction/response does feed into a vicious circle, augmenting what was previously more of an emotional/psych issue, and the problem needs to be addressed on not only a cognitive/emotional front, but a physiologic front as well.

    It’s been many years since that time, but one thing I did find when recently starting to consume a variety of fermented foods recently is that I am able to sleep better at night.

    What you have presented could be a the whole of helping someone’s depression, or it could be an important part. Thanks for helping us to consider the gut along with this issue.

    • TechnoTriticale

      re: … when
      starting to consume a variety of fermented foods recently is that I am
      able to sleep better at night.

      A deliberate 60 day course of quality probiotic, plus the permanent addition of ~20 grams prebiotic fibers daily, might amplify that.

      Other material factors include endocrine imbalance and environmental circadian disruptors.

      The big endo problem is thyroid, and the mis-testing, mis-diagnosis and mis-treatment of that (usually hypo) is a festering scandal.

      On circadian, take a hard look at the blue and bright light at night problem (easily addressed with blue blockers).

      • Lynn Dell

        I’m on Dr. Perlmutter’s probiotic for the next three months. Just started it 6 days ago. Am already taking in some hummus, and am thinking about putting part of a crunchy green banana in a smoothie now and then. Maybe raw potato. The idea of either does not thrill me, and I do like hummus.

        Regarding the thyroid, I’m in Dr. Davis’ Cureality community, where I quietly call myself “the Cureality village idiot.” There’s a lot to learn, and I am doing recitation work, as I find I can answer his multiple choice tests easily, but many crucial points are not sticking much in my long term memory yet. Dr. Davis has recommendations for getting the thyroid tests, which I plan on having done in May, along with other tests.

  • Lynn Dell

    Well, I have been taking your probiotic supplement for 6 days now. I already had been taking fermented foods and some prebiotic foods, and firmly believe they help with a better night’s sleep in my case. I think I noticed some increased feelings of calm and happiness upon starting the supplements, and a couple days into it I strangely began to feel resistive to something – as though there is a set point I have that I don’t want changed. Perhaps it is the probiotics beginning to alter something in the gut/brain connection. It’s not that I feel bad – I just feel different. I am planning on continuing these for a three month period.

    • Connie Zajac Dellinger

      I have had this “resistance” happen as well. I have not been able to overcome or move through it yet–I typically fall off the healthy protocol.

      • Lynn Dell

        Thank *you*. I am struggling with some increased anxiety due to a loved one being killed by a drunk driver years ago, and now having to teach our last one driving. Some months ago I fell hard on concrete with a slip on the ice. It took a minute to realize I was not severely injured, but I lost binocular vision and have some small amount of facial nerve involvement on the left side. The only reason I know it’s the facial nerve is I had to dissect it once upon a time and study its function. I feel disoriented, but no one but my eye doctor can tell anything happened to me. I’m still on the probiotics. Thanks for *your* reply – it helps me want to resurface so I can breathe again. 😉 Perhaps the probiotics have helped me to not be a complete basket case!

  • Bhrenda Drakeford

    Dr. Perlmutter. In my case I had a gastric bypass in 2006. My depression has worsened. Fiber would not benefit me because I can’t take the alot Ted water needed for fiber to be effective. What are some alternatives in my case as far as the supplements mentioned here?

    • David Perlmutter

      In our bypass patients we often find nutritional deficiencies. So you might want to ask your doctor to do a comprehensive nutritional analysis like the Spectracell test.

  • TeamDoctorsClinic
  • TeamDoctorsClinic

    He is right:

    blood-brain barrier vulnerability and cognitive/non-cognitive symptoms

    Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology.

    •Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity.

    • Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour.

    •Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain.

    • Thus, the emerging concept of a microbiota–gut–brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.

    John F. Cryan & Timothy G. Dinan Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior Nature Reviews Neuroscience 13, 701-712 (October 2012) | doi:10.1038/nrn3346

    • David Perlmutter

      I am loving this ! Just think of the possibilities moving forward!

  • TeamDoctorsClinic

    •gut microbiota drives immunoregulation, how faulty immunoregulation and
    inflammation predispose to psychiatric disease, and how psychological stress
    drives further inflammation via pathways that involve the gut and microbiota.
    •Rook GA1, Raison CL, Lowry CA. Microbiota, immunoregulatory old friends and psychiatric disorders. Adv Exp Med Biol. 2014;817:319-56. doi: 10.1007/978-1-4939-0897-4_15.
    Abstract http://www.ncbi.nlm.nih.gov/pubmed/24997041

  • TeamDoctorsClinic

    The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis.

    •Chronic infection alters gut function, including motility and visceral sensitivity, as well as feeding patterns, anxiety and depression-like behavior. These effects are likely immune-mediated, and involve changes in pro-inflammatory cytokines and altered metabolism of kynurenine/tryptophan pathways. Clinical studies have shown that chronic gastrointestinal infections lead to malnutrition and stunting, resulting in impaired cognitive function.

    •Both animal and clinical studies have demonstrated changes in behavior and brain chemistry after induction of intestinal dysbiosis (microbial imbalance) by administration of antibiotics.

    •Maybe we can try microbial-directed therapies to treat a broad spectrum of human conditions, including chronic gastrointestinal and psychiatric disorders.

    •Bercik P1, Collins SM. The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis. Adv Exp Med Biol. 2014;817:279-89. doi: 10.1007/978-1-4939-0897-4_13.
    Abstract http://www.ncbi.nlm.nih.gov/pubmed/24997039

    • David Perlmutter

      You are absolutely speaking my language

    • Sugarboo

      I’ve spent 4 years reading every research article about leaky gut. I am the perfect example of how gut health is what causes all the depression, most mental issues and many physical ailments. I’m a juvenile diabetic for 44 years now and have extreme leaky gut. I have to eat all home made organic food, nothing ready made from the store, and no chemicals etc.
      Within 24 hours of investing even 8 small non organic grapes( which have pesticides on them and in them) I end up a mental wreck for a week or more. Anything non organic has pesticides and even some organic foods that they lie about and claim they are organic. I’m going through it today, I had 8 grapes, 5 cherries, a piece of pear, and a piece of banana, yesterday around 7pm. Today I woke up feeling off and by noon, I mentally crashed and wanted to cry and take my life. It’s a terrible feeling. It doesn’t have to be fruit, it can be any non organic food. The pesticides kill too many good bacteria in my gut( and I don’t have many left) and cause all kinds of inflammation, and it’s that inflammation that affects me both mentally and physically. My feet hurt so bad I can barely walk, my finger feels like it was run over by a truck and won’t bend, and my ear/jaw hurts. This happens every time now that I eat a little non organic food. I have all the typical leaky gut gene mutations and I’ve taken everything I can to help heal m gut. But I can’t take L-glutamine because it gives me an excitory response in my brain and makes me sick and it takes 8 weeks to feel normal again.
      I have a right bundle branch electrical problem with my heart, so every time I take a knob biofilm buster , my hearts signal slows down or gets disrupted and I feel like I’m at deaths door. Too look at me, you would think I’m the picture of health!
      Depression is definitely caused by leaky gut or gut disbiosid… no doubt in my mind! When I’m feeling this bad like today, I do a 1/4 cup enema with distilled water and 2 sodium potassium butyric acid capsules, opened and poured into the water. I lay down and squeeze it in and stay there for 45 to 60 minutes or more. Within 30 minutes of doing it, my mentality changes I think why was I feeling so bad!?
      Butyric acid is food for the microbes that live in the mucosal lining of the colon. It has greatly changed how I feel and it’s amazing how my perspective on my life changes by the next morning when I get up. I AM a self made guinea pig and have experimented with so many things, hoping for a cure and better life. Unless you have had dinilitating mental issues, you could NEVER understand the behavior of someone WITH mental issues. It’s like I’m constantly in a glass ball, and watching people have a life, but I’m stuck in this glass ball observing and praying that one day I can fix this leaky gut and feel normal again. If you are reading this, go find a good source if ORGANIC, GRASS FED, beef bones and chicken feet and bones. Use a pressure cooker and cook them on Med-hi for an hour, then cool and add more water and cook for another hour. The next day all the good collagen and amino acids will firm a gel, and this is the best thing to eat daily to heal your gut. I live in a small coastal community in central Florida and you just can’t get organic grass fed beef bones. I’m about to drive to Minnesota!

      • Sugarboo

        Sorry that was so long!

  • gc11530

    Thank you for these short, informative videos.

  • Bhrenda Drakeford

    Thank you Dr. Perlmutter. I will do. Thank you for responding to my question. Bhrenda

  • James Byron


    Were you cast as an extra for the documentary “What The Bleep Do We Know?”

    Your Pal,

  • Glenn M.

    I saw that you recommend cyrex labs. I have used them before for my wife’s hashimoto’s. We put her autoimmune in remission her through nutrition. It took 18 mo. the last 6 mo we hit the right protocol. She’s now 14 mo in full remission, fully functional and back in high level training triathlon. What array or arrays do you recommend for LPS and other marker for ALS, MNDs, autoimmune conditions? This is for friend (67yr Male) recently diagnosed with ALS 3 wks ago. upon diagnosis I implemented nutrition protocol to help “leaky gut”. no advancement of ALS symptoms so far.

  • MK

    I just came across your website while searching for non soy products… It’s upsetting that together with gluten they are found practically everywhere. I’ve been on a gluten free diet for a year now and my Keratosis Pilaris skin looks much better. Definitely will buy your Grain Brain book soon, thanks for the informative website. People need more awareness in what they put in their system, most of the items in the supermarkets are toxic and these big corporations are poisoning people, it’s time to wake up and be proactive and pro aware!!!

  • Plants with peso

    I thoroughly agree that the gut-brain axis and our gut biome is a huge factor in both depression and obesity- which are highly correlated.

    The amount of antibiotics and bacteria in our animal-based food supply is appalling. Animals, particularly poultry, raised in incredibly tight and unsanitary quarters leads to both high levels of bacteria and subsequent antibiotic use. So its a no-win, you are either consuming large amounts of endotoxins (bacteria) or antibiotics that lead to weight gain, gut permeability and depression and possibly many other immune related diseases: cancer, auto-immune diseases etc…

    Food Inc. is a great documentary giving insight to just some of these vital issues to your food supply and health.

    • Geckotreefrog

      Not necessarily a no win. Eating grass/ pasture fed meat (rather than conventionally raised) is crucial for antibiotic avoidance & Vastly improved/ different fatty acid profile. These animals are also far more likely to be raised in humane conditions.

      • NYC

        Just as expensive as all the Functional Medicine practitioners. So if you can’t afford it, guess you can just get sick and die. Great medical model.

  • Christine

    can a gluten free grain be consumed with a bean and a green? I was taught this was a complete protein? So it is still considered a carb?

  • Millan Eriksson

    Dear Dr Perlmutter,
    I have for several years had a predominantly low carb diet. However sometimes I think that I can eat carb foods without trigging my suger cravings. This always fails of course. It almost always starts with me having something innocent as rice or even certain vegetables but soon I will eat bread, fries and eventually sweets and chocolate. This only takes two or three days of a fast spiralling descent in to sugar hell. I say descent as this is always combined with a descent in mood and energy aswell. It all goes hand in hand.
    I understand of course that if I eat bad food, I wil feel bad, nutrient levels would most likely not be as beneficiary for my body. But I am however astounded of how fast I fall into a depressed state. After just one week I will feel lethargic, drained of energy even, moody, and I will loose my otherwise cheery disposition and only see the negative in things. When I finally get my act together and cut out all ( well, not quite, but very low carb anohow) carbs I will see a drastic change in just 48 hours. I suppose the change is equally fast in the opposite direction when I eat carbs but I really don’t notice that until it’s really bad.

    I always eat a gluten free diet as I have coeliac disease so I wonder if the carbs in it self can trigger this in me and if a leaky gut is/could be the cause of this. I have just recently understood the connection between my mood and what I eat and reading your articles made me think that this was just what I am experiencing.

    I would just love some feed back.


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  • NYC

    What about the role of glyphosate on the gut?: https://drpompa.com/additional-resources/health-tips/the-dangers-of-glyphosate-an-interview-with-dr-stephanie-seneff

    “Glyphosate and the Gut

    How does glyphosate affect the gut and the human microbiome? Glyphosate not only pokes holes in the gut lining, but it also opens up the tight junctions of the intestines (a barrier
    that protects our gut from foreign invaders and keeps nutrients intact for proper digestion), thereby allowing undigested food particles to cross into the bloodstream. This opening creates the ability for antibodies to be made against all these food particles. And this can lead to both food allergies and leaky gut syndrome ..

    According to Dr. Seneff, if gluten molecules are in the presence of glyphosate, gluten digestion is blocked. Normally, the digestion of gluten involves crosslinks on different amino acids, but glyphosate stops those crosslinks from happening.”

  • Joe Vegazo

    Thank you Dr. Perlmutter for being a nervous system physician that is looking at major depressive disorder from a holistic/functional perspective. I have been dealing with severe MDD for 26 years and have tried all the medications, as well as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), and I am here to tell you that mainstream medicine does not know the true physiology of depression. This is why I follow what you have to say about depression (and other health issues), i.e., because you are interested in uncovering the true causes of disease. Unfortunately, mainstream physicians, especially psychiatrists, are not interested in learning the true causes of diseases. All they know is what drug or other mainstream treatment might help the symptom. Then when someone comes along, like myself, who has tried all the mainstream treatments and nothing has worked, they don’t know what to do because they have no true understanding of the disease in the first place. So again, thank you for looking at depression and other diseases from a holistic/functional perspective. Please keep doing what you are doing.

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