I posted this story up on Facebook a few weeks ago, but have decided – since the issue is so endemic – it’s worth a blog post, for those of you who missed it. When I was working as a nutritionist, the single most common complaints I got heard were constipation and gas/bloating. I was glad, then, to read the following study.
Most gas is caused by the fermentation of fibers by the gut bacteria. So while we’d all like to eat a really healthy plant-based diet, many struggle with it, from a digestive point-of-view. (I should mention that I would always tell clients looking to improve their diet to go slowly, as they added more fiber. It does take time for the bacteria to shift to those that can help you digest it better. And don’t forget to drink plenty of water, which also helps.)
In this study, 63 healthy adults received 3 days of a high fiber (residue) diet including legumes (beans, as you know, tend to cause gas); vegetables; whole grains; fruit…and then, were given 28 days of a fermented milk product which included lactic acid bacteria and particular species of Bifidobacterium animalis.[i]
To be eligible for the trial (as 63 people were), during the initial phase participants had have achieved at least 50% adherence to the flatulogenic diet and had a specifically measurable increase in flatulent expulsions. If they met criteria, they drank the fermented milk product twice per day for the aforementioned 28 days. (Previous research using this same product showed the same, but in that case, gas production was measured by breath test.) The results showed that the product reduced the feeling of needing to evacuate gas, the actual number of gas evacuations, and improved overall digestive wellness. It did not increase fecal microbiota diversity but it did increase the relative abundance of certain gut bacteria, which was measured in fecal samples given throughout the course of the study.
The lessening of flatulent evacuations was associated in an increase in the abundance of Mogibacterium and Parvimonas and a decrease in Desulfobibrionaceae. An increase in Succinivibrio and a decrease in Methanobrevibacter species led to a reduction in the feeling of needing to evacuate gas. (In case you are wondering (and I’ll admit, I was), gas was collected using something called a rectal balloon catheter, which we can all visually imagine. ‘nough said about that.)
As I am always looking for products to help with GI issues, I was encouraged by the study. As these authors write: “Our data may have also practical applications: high-residue diets have beneficial effects but are poorly tolerated and probiotics may enhance compliance to these healthy diets; conversely, probiotics may be indicated to reduce the side effects of dietary transgressions.” While I wouldn’t call eating a high fiber meal a “transgression,” I get their point!
For those interested, it took me awhile to track down the fermented milk product they specifically used. I found all kinds or research showing its beneficial effects, but in all these studies, it’s never actually named: it’s referred to as a “marketed” product, and that’s it. After doing my best Sherlock Holmes imitation, I was able to figure it out: it’s Activia, which is produced by Danone. As they say on their website: “Activia yogurt with Bifidobacterium lactis DN-173 010/CNCM I-2494, our exclusive probiotic culture, has been studied and shown to provide a specific digestive health benefit. Activia may help reduce the frequency of minor digestive discomfort.” I haven’t tried it myself so can’t attest to its taste but will give it a whirl once I can safely get into the supermarket!
[i] Le Nevé B, Martinez de la Torre A, Tap J, et al. A fermented milk product with B. lactis CNCM I-2494 and lactic acid bacteria improves gastrointestinal comfort in response to a challenge diet rich in fermentable residues in healthy subjects. Nutrients. 2020; 12(2), 320. doi: 10.3390/nu12020320.
The big (biome) buzz of the last couple of weeks: research just published out of Australia shows that the presence of a certain species of gut bacteria, Prevotella copri, in pregnant women protects babies from developing food allergies – at least within their first year.[i]
I have mentioned Prevotella bacteria in many posts over the last couple of months (for example, here and here). As a fermenter of fiber, it is present at higher levels in those who eat a plant-based diet…and thus, is found at lower levels in those who consume a typical “western” type diet, high in fat and sugar. It’s found at higher levels in the guts of most people living in ‘traditional communities”; and is non-existent or at very low levels in the vast minority of people living in developed nations. (Australia, by the way, has the highest rates of food allergy in the world.) The maternal microbiome has been shown in rodents to influence the rate of allergy in pups, particularly low levels of Prevotella.[ii]
In fermenting fiber, Prevotella increases levels of those short-chain fatty acids I write about all the time. In proper amounts, these are highly anti-inflammatory and play a big role in boosting levels of regulatory cytokines (which modulate inflammation). These scientists hypothesized that, “…it is plausible that low maternal carriage of Prevotella during pregnancy may be causally related to dysregulated immune development and high rates of allergic disease among children in westernized populations.”
The researchers analyzed data collected between 2010 and 2015 which looked at fecal samples from mothers at 36 weeks of pregnancy and then from their babies, at 1, 6 and 12 months of age. Children who had developed food allergy (58 in the cohort) were compared to those without (258 in the cohort).
They found that 20% of the babies that did not develop allergies had P.copri in their stool samples versus only 8% of babies with allergies: the presence of P.copri in the mom’s stool sample meant less risk of developing allergy for their baby. Only 1 mother with higher levels of the bacteria in her stool had a baby diagnosed with food allergy. Doubling the amount of P.copri in the stool meant an 8% drop in risk for the baby: “…maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring.” Remarkably, over 80% of the mothers in the whole database (over 1000 women) had no detectible P.copri in their stools.
While diet is the biggest factor in determining the composition of the gut bacteria, other environmental factors also play a role including antibiotic use and household size: as David Strachan, the father of the “hygiene hypothesis” predicted in 1989, more people in the house are thought to increase bacterial diversity within the family.
These scientists are now working to figure out whether or not it is safe to administer P.corpi as a probiotic during pregnancy to protect babies. Like everything having to do with the human biome, this is NOT a cut and dried kind of thing. The authors point out that 1 study has shown an association between P.copri and rheumatoid arthritis and another, in animals, showed that it may exacerbate colitis. Much of this may be dependent on the particular strain of the bacteria used. (Nothing is ever easy.) We’ll find out, I’m sure, as the research progresses.
This is pretty important work though as their findings would suggest that the absence of P.copri in the mother raises the risk of developing food allergy in the baby by more than 50%. That is just a remarkable finding.
I’ll conclude this post as they conclude their paper, as it sums up what we can do now perfectly: “In the meantime, our findings support the importance of antibiotic stewardship during pregnancy as well as a diet that optimizes the health of the maternal gut microbiome.”
[i] Vuillermin, P. et al. Maternal Carriage of Prevotella During Pregnancy Associates with Protection Against Food Allergy in the Offspring. Nature Community. 2020;11:1452. https://www.nature.com/articles/s41467-020-14552-1
I’ve illustrated this post with a picture of Janus, the Roman god of, among other things, duality. Every time I read about short chain fatty acids (SCFAs), I think of him.
Over the years, I’ve written about the benefits of SCFAs many times. (Here’s just one of many such examples.) I’ve also written about the massive amount of research that suggests that too much of a good thing, including SCFAs, are neurotoxic and extremely detrimental to health. (For example, here.)
I’ve commented before about how I find this idea of balance particularly interesting. SCFAs are critically important for good health as long as you have the right amount; and to make this even more complex, the timing is critical: they are good in the right amount at the right time. Just as excess levels are associated with disease, so are low levels. Since SCFAs are produced by gut bacteria, it’s easy to imagine how alterations in the microbiota can alter levels of these metabolites to influence the development of various illnesses.
The human biome is insanely complex.
A week ago or so, a paper was published in the journal, Cell, which explored how propionate (also called propionic acid, or PPA) “shapes” the course of multiple sclerosis (MS) by influencing the immune system.[i]
Like other autoimmune diseases, MS involves an increase in inflammatory immune cells and a decrease in regulatory ones (Treg, which modulate inflammation). This hyper inflammatory response leads the body to mistakenly attack the myelin sheaths of nerve fibers, which is a protective layer surrounding the nerves. This hampers the ability of nerves to send and receive signals properly.
In this study, the blood and stool of almost 300 people with MS were examined: the results showed low levels of PPA, no matter what type of MS the person had (i.e. relapsing-remitting, progressive, etc.) The bacterial species which produce PPA were found at lower levels; bacterial species associated with disease, like Shigella, were found to be at higher levels. The microbiome composition of the MS patients also varied according to the course of their disease, and this paralleled the fact that those newly diagnosed had the lowest levels of PPA, “…indicating that alterations in the gut microbiome might affect the severity of MS and that successful interventions might involve restoration of gut homeostasis.”
Thus, these scientists hypothesized that supplementing PPA, with its anti-inflammatory capabilities, might have a beneficial effect on those with MS, the hope being that the metabolite could boost levels of regulatory cytokines. 91 patients and 24 controls were given 1000 mg of PPA daily for 14 days. After these 2 weeks, Treg (including IL-10, one of the most important) rose by 25% in the control group and by 30% in the MS patients. 52 patients continued to take the PPA after the study concluded, and the improvement in Treg remained. This experiment was repeated in a 2nd group of patients and the results were the same. To boot, high levels of pro-inflammatory immune cells dropped significantly.
Long-term PPA supplement use was also studied. 41.2% of those on PPA had a lower annual relapse rate; 47.4% had a stable relapse rate; 11.3% had an increased rate of relapse. And one more interesting finding: 22 patients, who remained on the PPA for a year and a half, underwent brain MRIs: “…the striatum, a region known to shrink (brain atrophy) in MS, actually increased in volume compare to scans taken before starting this treatment.”[ii] This correlated with an improvement in clinical symptoms: “This improved Treg cell function correlates with alleviation of clinical symptoms in MS patients. In a retrospective setting, we observed a decrease in relapse rate and stabilization of disability during long-term [propionic acid] supplementation.”
By the way, no adverse effects to the PPA supplementation were reported.
The researchers conclude that their study saying that it “…provides further evidence of the hypothesis that SCFAs are reduced in autoimmune diseases, such as MS, as a consequence of an altered gut microbiome.… [PPA] supplementation had a beneficial effect on immunological, neurodegenerative, and clinical parameters in MS patients, including relapse rate and disability progression.”
This is very preliminary research, so rest assured, I will follow it. This this may well apply to other autoimmune diseases and help many people.
Today’s post describes what may be a critical finding in defining at least one mechanism whereby gut microbes directly affect the brain. Those interested in developmental disorders, like autism; Parkinson’s; Alzheimer’s; chronic fatigue; etc. should pay particular attention as, according this article, this information is likely applicable to those illnesses, and many more.
The relationship of neurological disorders to the gut bacteria is well established, as you know. This includes the developmental disorders and diseases mentioned above, as well as the development of anxiety, depression, etc. However, “…evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive.” Thus, it’s a major step forward that scientists at the University of Glasgow have discovered two new molecules that are produced by gut bacteria and that can travel directly to the brain, crossing the blood-brain barrier.[i] These molecules structurally greatly resemble carnitine, a compound derived from amino acids, which is critical in transporting fatty acids into the mitochondria of cells, where the fats are “burned” to produce energy. In looking like carnitine, these molecules essentially take the place of the real compound, thereby preventing real carnitine from performing its essential functions, “…leading to inhibition of brain cell function.”
These 2 molecules appear to be made by certain members of the Clostridiales family (C. clostridioforme and C. symbiosum). The authors of this paper theorize that these bacteria produce these “fake carnitine” molecules to give themselves a competitive advantage against species that do poorly in the presence of carnitine. Not much is known about these two species, except that their presence “…in the gut microbiome is associated with low microbial diversity, while C. symbiosum presence could further distinguish obese from lean participants.” We also know that these 2 strains are increased in the guts of those with autism, and completely absent in controls in studies comparing the two populations.
Mitochondrial dysfunction is well established in autism, as well as in Parkinson’s and Alzheimer’s. In autism, carnitine has been looked at as a potential treatment for a subgroup of those on the spectrum. A 2019 paper states, “Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency….Some people with autism (less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with L-carnitine is beneficial.”[ii] Another 2019 review describes the few clinical trials yet done on the population, which, while small, also showed consistency in results: there was improvement, often significant improvement, in the symptoms of autism. (The doses and duration of treatment varied greatly in these trials, so the fact that there was general consensus as to the benefits of carnitine treatment, I’d think, make the results that much more significant.)[iii]
In digging around, I also found that some evidence of carnitine’s protective role in Parkinson’s, heart disease, type 2 diabetes, etc. I also found studies linking low levels of carnitine with depression and anxiety.
Back to autism for one last thought: as you know, from reading my many posts (two of many examples, here and here) on the work of Dr. Derrick MacFabe and others in the field, the short-chain fatty acid, propionate (PPA) is now generally accepted to play a significant role in the development of many cases of autism. Abnormal gut bacteria, which includes high levels of clostridia (PPA producers, as well as the producers of these carnitine-like molecules), in the population – possibly combined with food sources (PPA is a common preservative) are likely to blame. High levels of PPA cause a reduction in carnitine levels: “PPA is thought to affect mitochondrial fatty acid metabolism by sequestering carnitine.”[iv] So now we are faced, thanks to this altered gut microbiota, with both a reduction of carnitine levels and these carnitine-analogs which replace what little carnitine is available, further destroying normal mitochondrial function. This, in turn, affects the way energy is produced in the cell and thus, the way the brain develops and functions.
Animal (dairy, meat, fish) products contain carnitine. If you tend to avoid these in your diet, and are among the susceptible population, you may want to consider supplementation. (Of course, talk to your health care practitioner first.) Carnitine (best taken in the form acetyl-l-carnitine) is a very low risk supplement. Only in high doses, 3000 mg per day or more, can it have side effects including nausea and vomiting. Strikes me that this may be another can’t-hurt-could-help kind of thing.
[iv] Thomas, RH, Foley, KA, Mepham, JR, Tichenoff, LR, Possmayer, F, MacFabe, DF. Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. Journal of Neurochemistry. 2010;113:515-529. oi: 10.1111/j.1471-4159.2010.06614.x
I’ve been keeping an eye out for anything new and interesting in the realm of the biome and arthritis – any kind of arthritis. Following are some highlights from a recent article on the two way communication between the gut immune system and the resident bacteria, and its association to rheumatoid arthritis (RA), osteoarthritis (OA), and inflammatory spondylitis (SpA) conditions like psoriatic arthritis and ankylosing spondylitis.[i]
The authors start by emphasizing that while exact mechanisms of action are as yet unknown, evidences continues to mount that these illnesses are directly related to alterations in the gut bacteria, and that those alterations are may well be causative.
These authors conclude that it is now clear that “…unfavorable dysbiosis-mediated immune alterations precede the development of these disorders, suggesting causal relationships in this link [between the microbiota and the immune system].” This is exactly the same phenomenon I described on Tuesday, seen in those with Parkinson’s.
We have to hope that soon there will be regular testing of our biomes. Perhaps if we can catch these changes early on, someday soon we’ll be able to prevent all these diseases from developing in the first place.
[i] Kalinkovich, A, and Livshits, G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropaties. Seminars in Arthrisi and Rheumatism. 2019; 49 (3), 474-484. DOI: 10.1016/j.semarthrit.2019.05.007
I haven’t given you a Parkinson’s-and-the-biome update in several months now, and as yesterday I read a great review of the current status of our knowledge on the connection between the two, I figured it was time.[i]
I am sure that most of you are very familiar with Parkinson’s Disease (PD), which is the 2nd most common neurodegenerative disorder after Alzheimer’s. We have known for several years now, that it appears that the disease starts in the gut, although the exact mechanism of action is still unknown. It seems, reading this paper, that the generally accepted (simplified) scenario right now is the following:
An unknown pathogen damages the nerves of the GI tract, resulting in the mis-folding (distortion) of a protein called α-synuclein (also known as Lewy bodies or Lewy neurites). These Lewy bodies first accumulate in the gut. Through various mechanisms, including the vagus nerve (which connects the brain to the gut’s nervous system), they move into the brain, including the substantia nigra, destroying the dopamine-producing cells there, resulting in the symptoms of the disease.
There is a large body of research now supporting this model:
If this subject particularly interests you, as it does me (seeing as I have multiple friends who have developed the damn disease in their 40s and 50s – INSANE), take some time to check out some of my other posts on the subject. There are a lot!
[i] Yang, D, et. al. The role of the gut microbiota in the pathogenesis of Parkinson’s Disease. Frontiers in Neurology. 2019. DOI: 10.3389/fneur.2019.01155.
My regular readers know that I am always on the lookout for “things you can do now,” and that I get very excited when I find something that actually makes sense, even if it’s not entirely proven or the mechanism of action fully understood. Yesterday, I came across research out of the University of Texas looking at the effects of eating mango on inflammatory bowel disease.[i]
Besides, it is one of my all-time favorite foods, so it’s a pleasure to wax lyrical on the delight that is a ripe mango.
Believe it or not, something as simple as eating 200-400 grams (approximately 7-14 ounces) per day of mango appears to make a measurable difference in alleviating the symptoms of inflammatory bowel disease (IBD). These researchers conducted a small pilot study on 10 volunteers (3 with Crohn’s disease and 7 with ulcerative colitis, all currently on drugs for their illnesses) with mild to moderate IBD, and had them eat mango daily for 8 weeks.
Their justification for the research: mango contains polyphenols, natural plant compounds that act as antioxidants, and have been shown in many studies to protect against cancer and other diseases. Some of the polyphenols you may be familiar with include flavonoids and phenolic acids. Their presence is one of the reasons a plant-based diet is so healthy. Previous studies have shown that mango polyphenols “…possess anti-inflammatory, anti-obesogenic [obesity] and anti-cancer activities, indicating their potential in modulating risk factors for intestinal disease.” In animal studies, in which colitis has been chemically induced in rodents, a mango-based beverage attenuated inflammation.
Results of this study:
Obviously, this was a tiny study (it was only a proof-of-concept, after all), so the results should be interpreted with caution. Still, it is nice to report some good news. I don’t have IBD, but what the hell?! It’s not like you have to twist my arm to convince me to eat my mango daily.
[i] H. Kim, V.P. Venancio, C. Fang, et al., Mango (Mangifera indica
L.) polyphenols reduce IL-8, GRO, and GM-SCF plasma levels and increase Lactobacillus species in a pilot study in patients with inflammatory bowel disease, Nutrition Research(2020), https://doi.org/10.1016/j.nutres.2020.01.002