The Two Faces of Candida

As you know, I like to keep up on research on all the different components of the human biome, so yesterday,  I read an article in the International Journal of Medial Microbiology about fungi.[i]  There were a bunch of really interesting facts which I’ll bullet point for you.

  1. Research until our fungi has trailed way behind research into our bacteria, but that is rapidly changing as science shows us more and more that these organisms have a profound effect on our immune systems, especially the induction of T helper cells which are, “…central orchestrators of protective immune responses.”
  2. Fungi are actually pretty hard to study for many technical reasons including, for example, the fact that they are surrounded by thick walls making our current DNA sampling methods less than optimal.
  3. Thus far, research shows that there are likely hundreds of different kinds of fungi in our biomes. There is, therefore, “…no consensus yet on which fungi constitute a ‘core gut mycobiome’.”
  4. Candida albicans is the major fungal species of the human gut, and is generally considered a commensal organism. However, like many other organisms I’ve talked about on this blog (like B. fragilis and Akkermansia), it has its negative side too.   It can invade almost every internal organ and for those who are immune suppressed, it can cause life-threatening infections.
  5. The finding that fungi are major inducers of T 17 helper cells is a major finding and it turns out that C.albicans is one of the most important in that regard: “Dysregulated Th17 responses contribute to local inflammatory disorders, such as inflammatory bowel diseases…” and “…a growing body of literature connects alterations in the gut fungal community to these inflammatory diseases.”   I’ve written about this before on this blog.  See here and here.
  6. We have known since the 1960s that antibiotic use resulted in the overgrowth of Candida, “…presumably due to the dampening of the competing bacteria.” It turns out that antibiotics actually alter the fungal community as well:  targeting bacteria can cause not only bacterial dysbiosis, but fungal dysbiosis as well, so closely linked are these two components of the biome.   C.albicans has been shown to impact the reassembly of the bacterial microbiome after antibiotic use and in fact, fungal dysbiosis is known to reduce the efficacy of fecal transplantation for C.difficile infections.
  7. Current research shows that C.albicans has a “duel” role: it is both a commensal that can protect its host from bacterial pathogens but is can also be a fungal pathogen itself, from which the host is protected by immune responses elicited by our commensal gut bacteria.

The authors point out that we desperately need research into the mycobiome to answer both the question of what belongs there and what do these organisms actually do there.  We know very little at this point.  But it was news to me that C.albicans – which I’d always thought of as a pathogen (who hasn’t heard of the nightmarish “yeast infection”?) may actually have a whole other beneficial side to it.  I find myself, yet again (for about the billionth time), amazed at the complexity of the human biome.

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[i] Pérez JC. Fungi of the human gut microbiota: Roles and significance. Int J Med Microbiol. 2021 Apr;311(3):151490. doi: 10.1016/j.ijmm.2021.151490. Epub 2021 Feb 25. PMID: 33676239.

The Price for a High Sugar Diet Early in Life – Memory Issues Later

Today’s post is about interesting research out of the University of Southern California, UCLA and the University of Georgia, looking at the relationship of sugary drinks early in life to cognitive issues later on.[i]  Here’s a fact that I didn’t know:  according to the CDC, sugary beverages are the leading source of added sugar in Americans’ diets and nearly 2/3rds of young people in the country consume at least 1 of these drinks every day.[ii]  Astounding, right?

The scientists gave adolescent rats unlimited access to sugar-sweetened beverages, proportionally comparable to what humans drink in both sugar content and calories.  When the rats grew to adulthood, their memories were tested using different methods:  one test looked at memory associated with the hippocampus and the other looked at memory associated with a brain region called the perirhinal cortex.  The hippocampus is known for its “…role in spatial and episodic memory, as well as for learned and social aspects of food intake control…” and is thought to be “…particularly vulnerable to the deleterious effects of Western dietary factors.”

They found that compared to controls, the rats that consumed the sugary drink scored much worse on memory tests involving the hippocampal region:  “During the juvenile and adolescent stages of development, a time when the brain is rapidly developing, consumption of diets high in saturated fat and sugar or sugar alone impairs hippocampal function”

But wait, there’s more.  The researchers then took a look at the bacterial microbiome composition of the rodents and found some major differences.  The sugar-drinking rats had bigger populations of two particular species, Parabacteroides distasonis and Parabacteroides johnsonii.

They took this information to the logical next step:  without drinking sugar, could these bacterial species on their own affect the hippocampal memory?  The scientists grew the species in their labs and then transplanted them into adolescent rats that drank plain water.  Sure enough, the rats that got these transplants showed memory impairment in the hippocampus as adults. What’s really interesting is that these “transplant rats,” as opposed to the ones who drank sugary beverages, had memory impairments in the perirhinal cortex as well, clearly demonstrating that gut bacterial alterations can affect brain function:  “These findings are consistent with previous literature in showing that early life consumption of Western dietary factors impairs neurocognitive outcomes, and further suggest that altered gut bacteria due to excessive early life sugar consumption may functionally link dietary patterns with cognitive impairment.”

In both the “transplant” rats, and the ones who actually drank sugary beverages, the scientists found that gene activity changed in those that control how nerve cells transmit electrical signals to other nerve cells.

The researchers plan to test, in future work, whether or not switching to a healthier diet can reverse this harm to memory caused by early consumption of high levels of sugar.  In the meantime, this is – pun intended – some serious food for thought.

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[i] Noble, E.E., Olson, C.A., Davis, E. et al. Gut microbial taxa elevated by dietary sugar disrupt memory function. Transl Psychiatry 11, 194 (2021). https://doi.org/10.1038/s41398-021-01309-7

[ii] https://www.eurekalert.org/pub_releases/2021-03/uosc-rsh033021.php

Feelings and the Microbiome: How Wisdom and Loneliness Affect Microbiota Health

I’ll lay off the prebiotics for today, and give you something completely different, to start off this new month.

We all know by now about the bi-directional relationship between the brain and the gut.  I’ve talked about it plenty of times on this blog, in relation to depression, stress, anxiety, PTSD, autism, schizophrenia, eating disorders, and more.  Today, I’m reporting on research out of the University of California which looked at the relationship between loneliness, wisdom and the bacterial microbiome.[i]

Let me give myself a pat on the back here.  Back in June, 2018, I wrote a post about healthy aging and the microbiome. Since we’re all getting older, it’s a topic that I follow pretty closely!  Anyway, the paper I talked about in that post was about risk factors for developing age-related illnesses.  After I went through what the paper listed, I wrote, “One factor the article does not mention that I would be willing to bet is a huge factor in the elderly is loneliness.”  I then described a paper I’d read recently on how loneliness is associated with an increased risk of mortality.  It doesn’t surprise me:  humans are social beings and isolation is a massive form of stress.  As the author’s of today’s paper start  off by saying, “Loneliness and wisdom have opposite effects on health and well-being. Loneliness is a serious public health problem associated with increased morbidity and mortality.”

So back to today’s paper:  these researchers note that wisdom has been shown to be associated with health and well-being, and that they have consistently found a strong negative association between loneliness and wisdom.  (Wisdom, they define, as a “multifaceted human characteristic with affective (or compassionate), reflective, and cognitive dimensions.”  Included in this, they list empathy and acts of compassion, self-awareness, and a comprehension of the deeper meaning of life events.)  Thus, they were curious how this all ties into the status of the gut microbiome…which of course, makes perfect sense.

They surveyed 184 adults, ages 28-97, living in community housing and measured, via self-report, their feelings of loneliness, wisdom, compassion, social support and social engagement.  They also collected fecal samples.  The results will come as a surprise to exactly no one:  the lower the level of loneliness and the higher the level of social support, compassion, wisdom and social engagement, the greater the richness and diversity of the gut bacteria.

The gut microbiome has already been associated with personality traits such as neuroticism, openness, agreeableness, and conscientiousness, as well as stress, empathy and emotional well-being.  Research has also shown a relationship between the bacterial microbiome and social behavior:  we already know that people with larger social networks have more diversity in their gut bacteria.

In their discussion the authors point out that, “It is possible that loneliness may result in decreased stability of the gut microbiome and, consequently, reduced resistance and resilience to stress-related disruptions, leading to downstream physiological effects such as systemic inflammation… Thus, lonely people may be more susceptible to developing different diseases.”  Social support, compassion, wisdom then may, “…confer protection against loneliness-related instability of the gut microbiome. Prior evidence suggests that perceived social support may buffer the negative effects of chronic stress on pro-inflammatory markers.”

Of course, as this is a bi-directional relationship, it’s also possible that social behavior is dictated by the gut microbiome.  This has been definitevely established in animal studies, but not as yet in humans.  Still, the future is promising in terms of being able to treat destructive feelings, like loneliness, by manipulating the microbiome:  “This evidence presents the exciting possibility that future ‘psychobiotics’ may be a novel therapeutic option for behaviors like loneliness….the findings represent a step forward in understanding the relationships between the gut microbiome and psychosocial factors that have important consequences for health and well-being.”

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[i] Tanya T. Nguyen, Xinlian Zhang, Tsung-Chin Wu, Jinyuan Liu, Collin Le, Xin M. Tu, Rob Knight, Dilip V. Jeste. Association of Loneliness and Wisdom With Gut Microbial Diversity and Composition: An Exploratory Study. Frontiers in Psychiatry, 2021; 12 DOI: 10.3389/fpsyt.2021.648475

Short Term Increase in Prebiotic Fibers Makes a Big Difference

I’m on a bit of a fiber kick right now!

A study just came out of the University of California, Irvin, which caught my interest.  Did you know that on average, Americans eat way less than 50% of the recommended daily intake of fiber?   And that low fiber intake is associated with type 2 diabetes, heart disease and colon cancer?  (Well, you knew the colon cancer ‘cause I put up a post on it yesterday on the Biome Buzz Facebook page, which I’m sure you all look at daily…)  According to this article, “A profound decrease in the consumption of dietary fiber in many parts of the world in the last century may be associated with the increasing prevalence of type II diabetes, colon cancer, and other health problems. A typical U.S. diet includes about 15g of fiber per day, far less fiber than the daily recommended allowance. Changes in dietary fiber intake affect human health not only through the uptake of nutrients directly but also indirectly through changes in the microbial community and their associated metabolism” [i]

I’ve talked about this multiple times on this blog – how little fiber we consume in the industrialized world compared to preindustrial societies, where people typically consume 60-120 grams per day!  I was FLOORED when I read, in this paper, that in one study, exchanging a low-fiber western-type diet in African-Americans for a rural African high fiber diet (at least 40 grams per day of fiber) led to a “significant decrease in precancerous biomarkers.

And how’s this for a timely COVID-pandemic-era fact:  did you know that dietary fiber has been shown to protect against influenza?  And may influence vaccine efficiency?!

This study was to assess what even a short-term increase in fiber could do for the gut bacteria and metabolite production. The subjects: students in an undergraduate biology course.  The subjects were given 10 high fiber meals of unprocessed foods per week for 2 weeks.  During this time, they collected stool samples to track the fecal microbiome.  The students also recorded all their food consumption including macronutrients; they had to reach a goal of 50 grams of fiber per day during the 2 weeks.

The researchers compared the bacterial composition as well as short-chain fatty acid production, as well as specifically running extra tests to look at levels of Bifidobacterium, which are known fiber degraders.  They found that this short intervention significantly altered the gut microbiome, including a sizeable increase in the levels of Bifidobacterium, as well as an increase in Lactobacillus.  Prevotella levels, which, as you know are associated with plant-based diets, also increased. They did not, however, detect a change in levels of short-chain fatty acids.  Still, the results were dramatic enough that the researchers want to conduct longer tests, and to learn more about how fiber intake can promote good health.

A side note from a summary of this research on News-Medical Net: the comments of the course instructor struck me as particularly interesting – how both she and the students were amazed by what foods were high in fiber, specifically noting berries, avocados, beans and legumes.[ii]   The students raised their fiber intake by an average of 25 grams per DAY…and several started from essentially zero grams of fiber per day. According to the professor, in participating in this research the students became extremely interested in what they were eating:  “”I think this experience will have a life-long impact on how we all look at nutrition labels.”  It’s really a shame how little about nutrition we are taught when we are young.

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[i] Andrew Oliver, Alexander., et al. (2021) High-Fiber, Whole-Food Dietary Intervention Alters the Human Gut Microbiome but Not Fecal Short-Chain Fatty Acids. mSystems. doi.org/10.1128/mSystems.00115-21.

[ii] https://www.news-medical.net/news/20210326/High-fiber-diet-can-significantly-alter-the-gut-microbiome-and-nutrient-intake.aspx

Prebiotics: What We Currently Know About Their Use in Neuropsychiatric and Neurodegenerative Diseases

One of the questions I get asked the most by my readers is “what prebiotic and/or probiotic is the best?”  Unfortunately, there is no good answer to that because we just don’t have the research to know.  To boot, everyone’s body is different.  Still, to help you all out as best as I can, I just finished reading a year-old paper on what we know about using prebiotics to treat anxiety, depression and cognitive issues.[i]  You’ll never believe it (ha!) but there are not even vaguely enough clinical trials to know how to optimize their use.  That said, there are some really interesting highlights in the paper and we can certainly conclude that prebiotics do play a potential role in helping alleviate symptoms.

The paper starts with emphasizing the fact that the main factor in determining the quality and quantity of microbiota is diet.  And we know that the microbiota is a fundamental regulator of both intestinal and brain health, and the immune system.  We also know that inflammation is one of the critical processes underlying several neurodegenerative and neuropsychiatric disorders including major depressive disorder (MDD), Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and many others.  Thus, the authors state, “…nutritional elements such as probiotics and prebiotics, could improve the host health due to their immunoregulatory properties.”

Probiotics and prebiotics that influence the brain are called psychobiotics.  I first wrote about that new term way back in 2016 – see here.  These can have anxiolytic (anti-anxiety) and anti-depressive effects, as well as altering cognition and emotions.  This particular article reviewed what we currently have in terms of research on the effects of prebiotics, which, the authors state, “…may be useful as a potential therapeutic tool for cognitive impairment, anxiety and depression.”

A quick review:  prebiotics refer to both digestible and non-digestible fibers that feed the microbiota.  Many foods are rich sources including onions, garlic, bananas, asparagus, and more.  Simply through eating a wide variety of fruits and vegetables, you are consuming a nice array of different prebiotics.  We know that by promoting the growth of beneficial bacteria, prebiotics help with the maintenance of the intestinal barrier and reduce circulating levels of inflammatory markers (including IL-6, TNF and c-reactive protein).  They can directly prevent the invasion of pathogens by “…decreasing endothelial adhesion due to their anti-adhesive property.”  I thought that was particularly interesting in light of that research I posted earlier this week, on a fungus that adheres to the inflamed and damaged tissue seen in Crohn’s disease, preventing wound healing.  Finally, prebiotics promote the grown of bacteria that produce stress neuromodulators as well as short-chain fatty acids, about which you have read a lot on this blog.  So, all in all, the right prebiotics have tremendous beneficial potential.

There are too many studies reviewed in the paper for me to go into them all so I’ll just give you a small sampling:

  1. “Several studies with prebiotics and AD have shown beneficial effects on cognition.” Chitosan oligosaccharides (COS) are anti-inflammatory, antioxidants, immune regulators and also have neuroprotective effect.  Studies have shown that they attenuate some symptoms of AD in animal models.
  2. Fructooligosaccharide (FOS), again in animal models, has shown positive neural effects, increasing levels of affected neurotransmitters (acetylcholine, serotonin, etc.) and decreasing damage to parts of the affected hippocampus. 6 weeks of administration in animals showed measurable cognitive improvements in the animals.  In a mouse model, it reduced neurodegeneration.
  3. Inulin, which is structurally similar to FOS, “…exhibits impressive results in cognition.” In humans, it has been shown to lead to “…greater accuracy in memory recognition and recall tests.”
  4. A recent clinical review of prebiotics showed that doses of 5-10 grams per day are safe and improve learning and memory and behavior. However, this was tested in young to middle aged people who are healthy.
  5. Prebiotics show some promise in MDD. FOS combined with GOS (galactooloigosaccharides) appear to possess antidepressant- and anxiolytic-like effects in rodents.
  6. Baker’s yeast beta-glucan, given for 12 weeks, reduced both upper respiratory infections as well as improved mood in stressed women, who are more susceptible to colds and other upper respiratory illnesses.
  7. Two capsules per day of the symbiotic (combination of probiotic and prebiotic), Familact H, was tested in a small double-blind and placebo-controlled trial, and showed efficacy in the treatment of moderate depression.
  8. 44 patients with irritable bowel syndrome (IBS), who also had anxiety issues, were given BGOS (bumono-galacto-oligosaccharides). This prebiotic is selective for Bifidobacterium, which improves lower gut health.  After being given either 3.5 or 7 grams of the prebiotic for 3 months, the patients showed, “…a significant increase in fecal Bifidobacteria and improvement in IBS symptoms, such as flatulence and swelling.”  They also all showed improvements on anxiety scores.
  9. Studies done on anxiety show that “…prebiotic administration leads to the amelioration or prevention of depression and anxiety.
  10. The authors conclude that “…prebiotics appear to be relevant candidates for the adjunctive treatment of anxiety and depression and cognitive dysfunction in neurodegenerative and neuropsychiatric diseases. Besides, these compounds can ensure healthy aging, retarding memory and learning loss in the elderly.”

Unfortunately, clinical studies are “scarce.”  Most, as you can see, are done on animals because of the overwhelming expense of human trials.  Still, I hope this post gives at least some guidance and/or ideas to those of you who would like to add prebiotics to your daily regime.

 

[i] Paiva IHR, Duarte-Silva E, Peixoto CA. The role of prebiotics in cognition, anxiety, and depression. Eur Neuropsychopharmacol. 2020 May;34:1-18. doi: 10.1016/j.euroneuro.2020.03.006. Epub 2020 Mar 30. PMID: 32241688.

Crohn’s Disease and the Mycobiome: A Fungus Prevents Wound Healing

I was amazed by new research out of the Washington University in St. Louis done in conjunction with the Cleveland Clinic.  Scientists discovered that a fungus called Debaryomyces hansenii, which is commonly used in the food industry to ripen the surfaces of cheese and processed meats, can latch on to injured and inflamed tissue in the intestines of patients with Crohn’s disease and causes the wounds to fester, leading to abdominal pain, diarrhea and bleeding.[i]

How was this discovery made? Using mice with intestinal injuries, the scientists attempted to find out why intestinal ulcers take so long to heal in people. They did DNA sequencing of the microbes found at the sites of these wounds and discovered that Debaryomyces hansenii is highly prevalent at that spot – but not at injured sites in the intestine.  When they introduced this particular fungus into mice with intestinal injuries, they found it slowed down healing, and giving the animals antifungal medication (Amphotericin-B) killed the fungus and allowed the wounds to heal.  This suggests, of course, that giving antifungals – along with dietary changes – may be a new way to promote wound healing in those with inflammatory bowel disease.

The researchers then looked at biopsies from 7 people with Crohn’s disease. They compared these samples to those from 10 healthy controls.  All seven of the people with inflammatory bowel disease had the fungus in their gut tissue while only 1 healthy person did.  They then looked at tissue samples from another 10 people with Crohn’s and found that the fungus was not only present, but was only found in inflamed tissue.  The first author of this study says, “If you look at stool samples from healthy people, this fungus is highly abundant…It goes into your body and comes out again.  But people with Crohn’s disease have a defect in the intestinal barrier that enables the fungus to get into the tissue and survive there.  And then it makes itself at home in ulcers and sites of inflammation and prevents those areas from healing.”[ii]

We know from prior research that the mycobiome plays a (possibly major) role in Crohn’s disease.  Back in 2017, in fact, I wrote about research that had just been presented at a conference in Chicago that showed that giving a yeast, C.tropicalis, (a normal part of the human mycobiome) to mice with Crohn’s markedly worsened the disease and adversely affected the composition of the bacterial microbiome.

Of course, before anyone makes any recommendations, this needs to be further studied in people.  Firstly, is there a connection between the consumption of certain foods, the abundance of this fungus in the intestines, and then flare ups of Crohn’s?  And can dietary modulation reduce the symptoms of Crohn’s disease?  Treating this fungus likely won’t be a cure for IBD, but it certainly may help alleviate symptoms and improve the quality of life for these patients. And you really do have to wonder what role the mycobiome plays in inflammatory bowel diseases.

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[i] Jain, U, et. al. Debaryomyces is enriched inCrohn’s disease intestinal tissue and impairs healing in mice.  Science. 2021. 371:6534(1154-1159). DOI: 10.1126/science.abd0919

[ii] https://www.genengnews.com/news/antifungal-drugs-and-dietary-changes-may-heal-gut-inflammation-in-crohns-disease/

L. reuteri and Immune Protection for Babies

Interesting new research on the relationship between the maternal microbiome and the immune system in infants was just published by in the Proceedings of the National Academy of Science[i].  Using a mouse model, scientists from the Virginia-Maryland College of Veterinary Medicine found that the particular probiotic bacterium Lactobacillus reuteri is largely responsible for raising the level of IgA antibodies in pups.

Gut bacteria can translocate to the mammary gland via the lymph system and blood.  Using a germ-free mouse model, the researchers found that “…Enrichment of certain maternal microbiota–derived bacterial taxa leads to early enhanced IgA production in the intestines, or what we refer to as IgA superinduction. In particular, L.reuteri was identified as a specific microbe derived from the maternal microbiota that colonizes the neonatal gastrointestinal tract to induce IgA.” It’s likely other bacteria do the same, but more research is needed to determine this.

IgA is produced mostly in the gut and is found at high levels there.  It’s the most prevalent type of antibody in humans and is largely responsible for protecting us from enteric (gut) pathogens; supplementing with it may protect infants from infection.  Because babies are born with only an innate immune system (the adaptive one – the one with memory, that involves antibodies to particular pathogens – develops over time), it’s important that they receive good immunity from their moms:  “Infants are prone to enteric infections due to an underdeveloped immune system. The maternal microbiota, through shaping the neonatal microbiota, helps establish a strong immune system in infants.”  One member of the research team states, “It’s not completely clear whether the observed immunological changes could affect autoimmune development, but if we can identify microbes that enhance early defenses without setting off self-reactivity, then we could potentially use them to protect infants from infections…”[ii]

Considering that L.reuteri seems to be pretty important as a potential probiotic for those with a wide variety of issues including autism, PTSD,  and autoimmune diseases (look here and here, for just a couple of examples of posts on the topic), it may be highly significant that it plays such a critical role in the early formation of the immune system. In fact, you should really take the time to check out this post on the role L. reuteri may play in teaching the body immune tolerance (i.e. how to distinguish self from non-self, and pathogen from not-pathogen).  I have to believe this is somehow all related.

In fact, in one of those coincidences that I love so much, as I was writing this post, I saw an article on using probiotics to increase intestinal diversity  in preterm babies.[iii]  These babies often suffer from life-threatening inflammation of the gut called necrotizing enterocolitis (NEC), which leads to the death of parts of the intestine – and often the death of the baby.  Prior research had shown that L. reuteri can reduce the risk of NEC in moderately preterm babies, and now, researchers in Sweden  found that it can do the same in extremely preterm infants, born between 23 and 28 weeks of pregnancy.  They tested this in 132 babies, none of whom weighed more than a kilogram (about 2 pounds), and found that those who received the probiotic (as opposed to the placebo) were less likely to be infected by pathogenic bacteria like Klebsiella an Staphyloccus, which can lead to NEC. At this point, the evidence is strong enough that probiotics are now fairly routinely given to preterm infants. L. reuteri just seems like a pretty good idea for moms and their new babies.

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[i] Mu, Q., et al. (2021) Regulation of neonatal IgA production by the maternal microbiota. PNAS. doi.org/10.1073/pnas.2015691118.

[ii] https://www.news-medical.net/news/20210303/Research-shows-a-causal-relationship-between-neonatal-antibody-production-and-maternal-microbiota.aspx

[iii] https://www.news-medical.net/news/20210311/Probiotic-supplements-increase-the-diversity-of-intestinal-bacteria-in-extremely-preterm-infants.aspx

Clear Pattern Emerges for Gut Bacterial Alterations in Parkinson’s Disease

Another step forward in sorting out the Parkinson’s disease (PD)/microbiome connection.  Researchers at the Quadram Institute in the UK conducted a meta-analysis of the gut microbiome in those with Parkinson’s disease.[i]  Prior to this work, there had not as yet been a consensus as to what alterations are definitively  associated with  PD.  Various studies have used different methodologies and to boot, there are inherent differences in the microbiomes of people around the world, shaped by lifestyles and diets.  For example, Lactobacillaceae has been found to be at high levels in those from the West, but this is never found in Chinese PD patients.  Another inconsistency:  many studies have found a depletion of species of Prevotellaceae, but many have not.

To overcome these inconsistencies these researchers reanalyzed the data from 10 different studies, and compared them to controls: 1200 samples collected from people in 6 different countries around the world.  This vast amount of data allowed them to see a clear pattern emerge:  “In agreement with previous studies, we show that the gut microbiome of PD patients significantly differs from those of controls.” Firstly, they confirmed that those with PD have low levels of butyrate-producing bacteria.  Remember that the short-chain fatty acid (SCFA), butyrate, is crucial in the health of the lining of the gut.  (You can read more about that here.)  Low levels of butyrate are associated with inflammation of the gut lining and increased permeability (i.e. leaky gut).  (Similar findings are found in patients with inflammatory bowel disease, and here is a fact that I did not know:  IBD patients have a 20-30% increased risk of developing PD.) From the paper:  “Butyrate and other SCFA are not only relevant for gut health, but they can also influence the enteric nervous system (ENS), have systemic anti-inflammatory properties, promote normal microglia development, and potentially affect epigenesis in the CNS.”

Secondly, bacteria which produce methane are at abnormally high levels in those with PD.  Thirdly, PD patients have an increased level of bacteria that degrade mucus.  The combination of these two findings might well explain the constipation issues that plague nearly everyone with the disease.  (In fact, as I’ve mentioned before, chronic constipation is one of the earliest signs of impending PD.)   To sum up, “Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations.”  Low levels of Lachnospiraceae and Faecalibacterium have been detected in other neuro-inflammatory and neurodegenerative disorders (including multiple sclerosis).  And Akkermansia, which is so often found to have probiotic properties, is another of those two-faced bacterial species we’ve seen in other species, like B.fragilis:  “Akkermansia has been repeatedly shown to be more abundant in PD compared to control. Akkermansia spp is considered beneficial for human health and is potential probiotics, as they fortify the integrity of the epithelial cell layer and can modulate the immune system. However, contrasting results regarding the influence of Akkermansia spp on gut health exist.Recently, safety concerns have been raised about the use of A.municiphila as a probiotic, as its enrichment in neurodegenerative diseases (e.g., Alzheimer’s disease, multiple sclerosis) could contribute to the progression of neural pathologies by degrading mucin, increasing gut inflammation and permeability and finally leading to higher endotoxaemia, and systemic inflammation.” (You can read more about that here.)

What is still unknown is cause and effect:  that is, do these microbiome changes precede the development of PD or are they the result of the disease?  More than that, can using probiotics, prebiotics, fecal transplant, etc. modulate the gut biome and attenuate the disease?  Or stop it from developing in the first place? Dr. Stefano Romano, the lead researcher, states, “The restoration of a balanced microbiome in patients might alleviate some of the symptoms of Parkinson’s, and this is a really exciting route of research we are exploring.”[ii]


i] https://medicalxpress.com/news/2021-03-parkinson-microbiome-links-gut-health.html

[ii] Stefano Romano et al. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation, npj Parkinson’s Disease (2021). DOI: 10.1038/s41531-021-00156-z

Microbiome Alterations by 12 Months and the Development of Behavioral Issues

One of the many subjects being studied that are of particular interest to me is the long-term effect of alterations to the early, developing microbiome.  There is little doubt at this point that at the very least, the bacterial microbiome, is a huge factor in the current epidemic of autism.  It likely plays a role in childhood asthma, ADHD, allergies, and many more illnesses.  As a first-hand witness to the effects of early antibiotics on behavior, I have followed this research very carefully for 25 years now.   Those first two years of life – especially so the first year – are critical in the establishment of normal, healthy microbiota.

A paper on how the gut microbiota develop during infancy, and how this may relate to future behavior issues, caught my eye a couple of weeks ago, and I finally had a chance to read it this week.[i]  There is not a lot of research on this topic yet, believe it or not.  Prior research had shown (in a cohort of 77 infants) an association between microbiome diversity and temperamental issues.  Another study noted an inverse association between bacterial diversity at 12 months of age and overall cognitive and language measures at 2 years old (i.e. the more diversity at 12 months, the lower the cognition and language scores at 2 years).  (This is interesting, as it’s the opposite of what you’d expect in an adult.  But as you know, from this blog post of a few weeks ago, what is healthy for someone at one age may not be at all healthy for them at another point in their life.  Of course, the results need to be confirmed in future testing.)

This study used an overall sample of 1074 infants, 201 of which had sufficient data to be included in the research.  Stool was collected at 1, 6 and 12 months of age, and infant behavior was analyzed using a couple of testing questionnaires.  At 2 year of age, 22 of the 201 babies were classified as cases with elevated behavioral problems.

The results show that in those with behavioral abnormalities, at 12 months Prevotella was detected only 4% of the time, whereas in those without behavioral issues, it was detected 44% of the time.  This is highly statistically significant.  This finding stood even when adjusted for other possible cofactors, like the baby’s sex, maternal smoking, household income, number of siblings, infant feeding practices, and so forth.  Not a surprise, the use of antibiotics between 9 and 12 months was associated with reduced Prevotella:  this was the “best predictor” of Prevotella absence.  (I have written about Prevotella many times on this blog.  We know it is more abundant in non-Western populations who eat much higher levels of fibers.  Generally speaking, it is regarded as a probiotic species.)

Antibiotic exposure prior to that 9-12 month period of time was not a predictor of lower Prevotella.  The authors hypothesize that this is because the microbiota have a chance to normalize, but exactly how diet and other environmental and internal factors affect reconstitution is unknown.  A lot more work needs to be done on how antibiotic use may be a factor in later developmental issues.

The authors conclude by stating that they have “…identified potential microbial targets for improving behavior, and factors which may affect them, such as antibiotic use.  This study adds support to evidence that the human infant gut microbiota may have long-term neurodevelopmental consequences, conferring protection or vulnerability to behavioral and mental health outcomes in later life.”

I often wonder what our lives would have been like had Alex not been given antibiotics at birth for 5 days and then again, for 2 weeks just before his 1st birthday.   While I try not to go there, it’s really hard sometimes, as the evidence mounts for the devastating effects on both brain and immunological development. This is one of the reasons I am so interested in research on other means of controlling bacterial infections (for example, bacteriophages (look here for example)).

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[i] Loughman A., Ponsonby A.L., O’Hely A. et al. Gut microbiota composition during infancy and subsequent behavioural outcomes. EBioMedecine. 2020; 52: 102640. https://doi.org/10.1016/j.ebiom.2020.102640

The Mycobiome, Diet and Weight

The big biome buzz over the last few days has been about research out of the University of Alabama at Birmingham which showed, in a mouse model, that the fungi of the gut – the mycobiome – plays a major role in how processed foods are digested and how body mass is distributed.[i]

To conduct this research, the scientists got genetically identical mice from 4 different labs, ensuring that their gut bacteria and yeasts were not exactly the same. Starting then with these diverse gut compositions, they measured the effects over time of dietary differences.  The mice’ diets were either standard chow or highly processed food made to resemble a typical American diet.  After 6 weeks, the researchers measured their body fat, as well as the genes and hormones involved in metabolism. They also analyzed the yeasts found in the foods themselves so they’d know what were from external sources versus what species were commensal.

What did they find?  Variations in the composition and abundance of the mycobiome determined host metabolism. Essentially “junk” food (highly processed foods) changed the composition of the fungi in the jejunum (part of the small intestine) in mice, which, in turn, led to metabolic changes: “Eating processed food made most mice fatter, but how much weight and how their metabolism changed varied between mice with different microbiomes.”[ii] Variations in the composition of the mycobiome, especially increased amounts of Termocyces and lower levels of Saccharomyces were the most strongly associated with metabolic disturbances and with weight gain (about 15% more).  Says the lead researcher, “”We showed that the gut mycobiome of healthy mice was shaped by the environment, including diet, and that it significantly correlated with metabolic outcomes…”[iii]

Next steps in this research is to look at humans and mice to learn more about how the mycobiome influences metabolism and weight gain in a high-fat diet and also, after weight loss surgery.  The scientists also hope to transplant human microbiomes into mice to see the effects.  Considering how little research has been done on the effects of the mycobiome on human health – and the effects of diet on the mycobiome – this is pretty exciting research:  “We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet.”

Still, yet again (for the billionth time), it struck me how insanely complex this all is.  Does diet directly dictate the composition of the mycobiome?  We know diet alters the bacterial microbiome – so does this, in turn, affect the mycobiome?  Or are both true? Time will tell.  I’ll be following these developments closely.

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[i] Tahliyah S. Mims, Qusai Al Abdallah, Justin D. Stewart, Sydney P. Watts, Catrina T. White, Thomas V. Rousselle, Ankush Gosain, Amandeep Bajwa, Joan C. Han, Kent A. Willis, Joseph F. Pierre. The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet. Communications Biology, 2021; 4 (1) DOI: 10.1038/s42003-021-01820-z

[ii] https://theconversation.com/fungal-microbiome-whether-mice-get-fatter-or-thinner-depends-on-the-fungi-that-live-in-their-gut-155942

[iii] https://www.sciencedaily.com/releases/2021/03/210305123802.htm