Inflammatory Bowel Disease, the Microbiome and…(ahhhh!) Mango

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:

  1. Scores of an assessment of disease activity (bowel frequency, stool consistency, abdominal pain, nausea/vomiting, etc.) improved: “…findings in this study indicated that 8 weeks of mango intake exert beneficial effects in slowing the progression and reducing the severity of IBD…”
  2. Levels of blood inflammatory markers associated with IBD significantly improved.
  3. Stool analysis showed marked improvement in the quality of the bacterial microbiome, with significant increases in Lactobacillus species, including plantarum, reuteri and lactis.  These species “…are known to possess anti-inflammatory activity in the treatment of colitis by down-regulating the secretion of TNF…and up-regulating IL-10.”  (TNF-alpha is a major player in the pro-inflammatory system; IL-10, as I have talked about many times on this blog, is a major player in the regulatory system, which turns off the inflammatory response when no longer needed.)
  4. The short-chain fatty acid, butyrate, significantly increased. This SCFA is associated with improved intestinal barrier function (i.e. improved leaky gut).
  5. One phenomena was noted, unrelated to IBD: “…daily mango intake seemed to have been associated with a slightly decreased calorie and fat intake.”  Now this may not seem all that interesting…except that it’s not the first time this has been noted in a study.  Several studies have shown the same, including one that noted a decreased trend in caloric intake in obese people.

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.

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[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

Bile Acids, Inflammatory Bowel Disease, and the Microbiome: A Rapidly Developing Story

Back in January, I wrote about how bile acids are regulators of inflammation and thus, when dysregulated (either too high or too low), this dysregulation can lead to disease.  Bile is produced by the liver and excreted into the intestines to digest fat.  Gut bacteria convert these primary bile acids into secondary bile acids, which are, in turn, immune signaling molecules, and I described research out of Harvard looking at the exact mechanism of action.  In that post, I also wrote about a second paper, also from Harvard, that looked at how diet and the gut bacteria work together to modify these immune-mediating bile acids.  I mention that “…low levels of bile acids make the mice prone to developing inflammatory conditions, like IBD.”

Well, new research out of Stamford University has zeroed in on a particular kind of bacteria missing from those with ulcerative colitis (UC) which may be responsible for the development of the disease.[i]  The study consisted of 2 groups of patients, 17 with UC who had undergone surgery to remove the colon and rectum.  The surgeons then reposition the lower end of the small intestine to create a pouch that acts as a rectum. Unfortunately, half of these UC patients develop a condition called pouchitis, which is inflammation of this pouch similar to the UC itself.  The second group of patients had a rare genetic condition which leads to that same surgery but almost  never develop pouchitis.  In comparing the two groups, they noted that those with UC had markedly lower levels of  both microbial diversity and secondary bile acids, including the two most prominent, deoxycholic acid and lithocholic acid, mirroring the Harvard research.  They noted too that the family of bacteria called Ruminoccoccaceae was significantly low in the UC patients versus the others.  These bacteria, along with several other kinds, carry the genes to create secondary bile acids.  Ruminococcaceae are a family of bacteria within the class of Clostridia.[ii]

In fact, when primary bile acids were incubated in stool samples from the patients with the genetic condition, secondary bile acids were created.  This did not happen with the same procedure using stool samples from the UC patients.  And in 3 different animal studies, when mice with IBD were supplemented with these 2 bile acids, markers for inflammation  markedly improved.

There is a phase 2 clinical trial happening at Stamford right now on 15 patients with UC who have had this pouch surgery; they are being given a naturally occurring secondary bile acid which is already approved by the FDA for other conditions.  I will absolutely keep an eye out for those results.  However, looking at Clinical Trials.gov, it looks like the primary completion date of the study isn’t until December 2025.  (I wish that there were a trial ongoing for those who have not as yet lost the bottom of their colon/rectum.  It would be great to see if this treatment could help prevent that horrible surgery in the first place.)

A postscript:  as I was getting ready to post this, I spotted breaking news about a brand new study out of Michigan State University about the discovery of brand new bile acids that are produced only by our gut microbes, not by our own bodies.[iii]  The discovery has apparently rocked the scientific world in that, no new bile acids have been found since their initial discovery in 1848:  “This discovery will change how medical textbooks address digestion, and it contributes to an ever-growing body of knowledge supporting the importance of the microbiome…”  And these new bile acids are “…particularly abundant in the guts of people suffering with gastrointestinal diseases, such as Crohn’s…”

This is really a developing story: the recognition of a completely altered bile acid composition in those with diseases involving intestinal inflammation.  Definitely stay tuned!

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[i] Sidhartha R. Sinha, Yeneneh Haileselassie, Linh P. Nguyen, Carolina Tropini, Min Wang, Laren S. Becker, Davis Sim, Karolin Jarr, Estelle T. Spear, Gulshan Singh, Hong Namkoong, Kyle Bittinger, Michael A. Fischbach, Justin L. Sonnenburg, Aida Habtezion. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host & Microbe, 2020; DOI: 10.1016/j.chom.2020.01.021

[ii] https://en.wikipedia.org/wiki/Ruminococcaceae

[iii] https://www.sciencedaily.com/releases/2020/02/200226131321.htm

Babies, Anxiety and the Gut Biome

Remember last Thursday, when I wrote about the relationship of the gut bacteria to the structure and function of the brain?    I mentioned in that post that, “In Western populations, Bacteroides and Prevotella species tend to dominate, with the former outnumbering the latter –as they did in this sample of women. A diet high in fat and animal protein (i.e. a standard Western diet) is more associated with higher Bacteroides species than Prevotella…”  I went on to point out that, “Prevotella levels are markedly higher in non-Westernized societies, which consume plant-based diets, where people are actually less prone to ‘mental’ illnesses like depression or anxiety. And don’t forget, low levels of Prevotella  have also been associated with leaky gut and also, Parkinson’s disease.  So the likelihood is that higher Prevotella amounts are better for health.”

With that fresh in mind, yesterday morning I spotted an article[i] that looked at the composition of the bacterial microbiome in infancy and its relationship to the development of anxiety issues in toddlers, and the findings should come as no surprise:  “…we found a clear association between decreased normalised abundance of Prevotella in faecal samples collected at 12 months of age and increased behavioural problems at 2 years…”

This finding held even when other variables were accounted for, like mode of birth, pet ownership, maternal smoking, breast feeding, and so forth.

The test group tested consisted of 201 infants, selected from an Australian birth cohort of over 1000 babies.  Stool samples were collected at 1, 6 and 12 months, and when the babies reached 2 years of age, their parents filled out extensive questionnaires.  No association was found in behavioral differences based upon the first 2 stool collections, but the 12-month sample found significant associations.  Believe it or not, Prevotella was found in only 4% of the children who went on to have anxiety issues versus 44% of the children without any problems.  (Lacnospiraceae species were also altered in the behavior group, although when other factors as mentioned above were accounted for, this was somewhat less significant.)

The main factor leading to lower levels of Prevotella? You guessed it: antibiotic use.  However, the behavior group’s antibiotic use was not different from the non-behavioral group with low levels of Prevotella, so this was not considered significant in terms of predicting behavior.

The mechanisms are still unknown but there are numerous possibilities:  stimulation of the vagus nerve, various enzymes or cytokines, tryptophan metabolism, the immune system, and so forth.  Studies are already underway to replicate these findings and to delve into causality.  The implications of this work may be huge:  as these authors state, this work “…adds support to evidence that the human gut microbiota may have long-term neurodevelopmental consequences, conferring protection or vulnerability to behavioural and mental health outcomes in later life…”  This work, therefore, may have tremendous relevance not only to anxiety disorders (which are on the increase in industrialized nations) and other mental health issues, but also autism (remember the fecal microbiota transplant study – FMT led to higher levels of good bacteria, including Prevotella, which is low in those with autism), and potentially illnesses that tend to hit in later life, like Parkinson’s disease.  It’s looking more and more like eating right from the moment of birth is crucial for long-term physical and mental health.

Hopefully there will be more to report to you in the near future.  In the meantime, eat that plant-based diet!

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[i] Loughman, A, et. al. Gut microbiotia composition during infancy and subsequent behavioural outcomes. EBioMedicine. 2020. DOI:https://doi.org/10.1016/j.ebiom.2020.102640

Your Brain and Your Microbiota…Which Forms Which?

This is a great follow up to my post on Tuesday about the relationship of personality to the gut bacteria.   Today I’m covering a new study from UCLA which looks at how the gut bacteria affect the actual structure and function of the brain.[i] Our understanding of the gut-brain axis continues to grow; it really is fascinating watching the slow but steady progress!

40 healthy women provided stool samples, and were then divided into two groups, based upon the composition of their gut flora.  33 of them had higher levels of Bacteroides than Prevotella; the other 7 had the opposite profile, with Prevotella-family bacteria predominating.

It turns out that their bacterial profiles were predictors of both the amount of gray matter in various parts of the brain as well as their reactions to different stimuli.

In terms of structure, “…white and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2% respectively.” That is, there was statistically significant correlation between the make-up of the gut bacteria and the structure of the brain. Women with higher levels of Bacteroides (versus Prevotella) had thicker gray matter in their cerebellum and frontal region which are “…involved in the complex processing of information” and more brain matter in the hippocampus, which is a big player in memory processing.  The Prevotella group had less brain matter in several regions including “functional and structural differences in the hippocampus” (which is the brain region involved in emotion regulation), as well as differences in areas involved with attentional and sensory processing.

This latter group of women, when viewing negative images, showed less activity in their hippocampus, and greater levels of anxiety and irritability than the Bacteroides group.

Of course, we still face a chicken-or-the-egg scenario in that it is currently unknown whether or not it is the brain dictating the gut flora or the gut flora dictating the structure/function of the brain. The authors point out that while “…some aspects of the microbiota’s influence on the CNS are likely to be established early as traits, other aspects may be malleable and are vulnerable to environmental factors…”  Timing too may matter:  what you eat long term, or during early years of life while the brain is still developing, may have lasting influence.  It does appear that diet is a major factor.  In fact, these researchers have already published work demonstrating that in healthy women, 4 weeks of ingestion of “…a fermented milk product with probiotics can shift functional brain responses to an emotional attention task…providing more direct evidence in humans that brain function can be affected by modulation of gut microbiota.”

In Western populations, Bacteroides and Prevotella species tend to dominate, with the former outnumbering the latter –as they did in this sample of women. A diet high in fat and animal protein (i.e. a standard Western diet) is more associated with higher Bacteroides species than Prevotella, which is associated with a plant-based diet.  With so few women fitting into the Prevotella group then, the authors advise caution in interpreting their results.  Much larger studies are needed to confirm whether this “…propensity towards developing a more negative affect during this paradigm is a marker of personality traits, a risk factor for developing clinically relevant negative moods states, or just a healthy variant.”

The interpretation that a plant-based diet (which leads to higher amounts of Prevotella than Bacteroides but also, a more negative emotional state under these laboratory conditions) is therefore less desirable is fallacious.  Someone’s emotional state may, in fact, dictate their diet.  I, for example, thought about a healthy diet a lot less when I was younger and hadn’t yet faced my son’s autism diagnosis.  Yes, I am under a great deal more stress but we also eat way healthier.  Prevotella levels are markedly higher in non-Westernized societies, which consume plant-based diets, where people are actually less prone to “mental” illnesses like depression or anxiety. And don’t forget, low levels of Prevotella  have also been associated with leaky gut and also, Parkinson’s disease.  So the likelihood is that higher Prevotella amounts are better for health.  (Wouldn’t it be interesting if they followed these women over the next 20 years to see how they fare, health-wise?!)  In fact, the structure of the brain in these women may not actually be caused by their gut bacteria, or these particular gut bacteria.  This is a correlation study, not a causation one.

As always, I will watch and wait to see further research on this.

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[i] Tillisch K, Mayer E, Gupta A, et al.  T, Zeevi D, Zmora N, et al. Brain structure and response to emotional stimuli as related to gut microbial profiles in healthy womenPsychosomatic Medicine. 2017. DOI: 10.1097/PSY.0000000000000493

Your Personality and Your Gut Bacteria: Mirror Reflections?

I posted the news last week on the Biome Buzz’ Facebook page, about research out of Oxford University in the UK[i] which connected personality type to specific microbiome patterns.  The story has gotten huge coverage in the world of the biome, so I reckon I better write about it in greater detail.  After all, you come here to get the latest news in detail, hot off the presses, right?

The study involved fecal samples from 655 adults (71% female, 29% male).  They all filled out a questionnaire which asked about lifestyle, health, behavior, and so forth.  The paper’s author, Katerina Johnson (from the Department of Experimental Psychology), then associated personality type (for example, sociability and neuroticism) to the gut bacteria in the samples.

The questionnaire used, the International Personality Item Pool, uses 50 items to group people into 5 personality types:

  • “extraversion, or the “propensity to seek and enjoy others’ company”
  • agreeableness, defined as “trust and cooperation in social interactions”
  • conscientiousness, or the “attention to detail and focus”
  • neuroticism, i.e., the “tendency to feel negative emotions”
  • openness, which researchers have described as “creativity, intellectual curiosity, and willingness to seek new experiences”[ii]

After adjusting the data for variables that might influence the composition of the bacteria (sex, age, BMI, birth delivery mode, infant feeding method, antibiotic use in the last 6 months, probiotic use), she was left with a pool of 261 qualifying participants.

The results were pretty remarkable:  “…both gut microbiome composition and diversity were found to be related to differences in personality.”

Those types of bacteria now associated with autism spectrum disorders proved consistent in that, in the general population, they were also found in less social people.  Those individuals with extensive social networks had more diverse microbiota, suggesting that social behavior is important for microbiome health. (We are social animals, after all, so this didn’t shock me.)  For example, Akkermansia (whose health benefits I have covered several times before, including here), Lactococcus and Oscillospira were “…found to be more abundant in individuals with a higher sociability score.”  This coincides with prior research which has shown that those with autism have a reduction in Lactococcus and Oscillospira, and 1 study thus far has found lower levels of Akkermansia as well.  In animal studies, Oscillospira has already been associated with social behavior, and both this species and Akkermansia, “…are associated with good health; Akkermansia has anti-inflammatory properties and there is some evidence it may be protective against metabolic disorders while lower levels of Oscillospira are linked to inflammatory disease.”

Also really interesting:  those who were less social behavior had higher levels of Desulfovibrio and Sutterella, the former of which I have covered in relation to autism in the past (see here):  “…in fact, it has been hypothesized that Desulfovibrio species may play an important role in the pathophysiology of autism.”

Another not-surprise: stress and anxiety reduced microbiota diversity.  And, as I have talked about in the past (see here), poor sleep quality also appeared to lead to a loss of diversity.

A few other important points:

  1. People who ate more foods with naturally occurring pro- and prebiotics had significantly lower levels of stress, anxiety and neuroticism, and proved less likely to develop a mental illness:  “Diversity of the gut microbiome was also related to the amount of food people consumed containing natural probiotics and prebiotics.”
  2. Remarkably, the research did not show the same for pro- and prebiotics in supplement form. This latter finding, however, may be because those who have been on antibiotics or who have gut issues – thus already likely having dysbiosis issues – are more likely to use supplements.
  3. This one is not a surprise. Those who were formula fed as babies had less diverse microbiota.

The author points out that the relationship of the gut microbiota and behavior is bidirectional and thus, “…the gut microbiome can affect the stress response and stress also disrupts the gut microbiome.”  We can assume then that improving one’s social behavior may have long-term health benefits.

I want to share Dr. Johnson’s concluding remarks as they are definitely worth your time to read:

“…it is pertinent to reflect on the ways in which our modern-day living may provide a perfect storm for dysbiosis of the gut. We lead stressful lives with fewer social interactions and less time spent with nature, our diets are typically deficient in fibre, we inhabit oversanitized environments and are dependent on antibiotic treatments. All these factors can influence the gut microbiome and so may be affecting our behaviour and psychological well-being in currently unknown ways.”

I couldn’t have said it better myself!

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[i] Johnson, KV-A. Gut microbiome composition and diversity are related to human personality traits. Human Microbiome Journal. 2020;15.  https://doi.org/10.1016/j.humic.2019.100069

[ii] https://www.medicalnewstoday.com/articles/can-your-gut-bacteria-predict-your-personality#More-friends-may-promote-gut-health

Coming Soon: Sports-Specific Probiotics?

Last September, the big news in the wonderful world of the biome was that Harvard was taking on designing probiotics to improve athletic performance: “The Wyss Institute for Biologically Inspired Engineering at Harvard University has announced that its athlete microbiome-based technology will be commercialized by Fitbiomics Inc., a recently formed startup company, to develop highly validated probiotics based on elite athletes’ microbiomes, which could improve athletic performance and, conceivably, even overall health.”[i]  (For all you major stud muffins out there, you can actually sign up now to beta test their product.)  I am really intrigued by this whole field of research.  After all, we have known for several years that elite athletes have biomes different from the rest of us mere mortals…and that exercise improves the quality of the bacterial microbiome.  You don’t have to be going to the next Olympics to reap the benefits of regular exercise.

I found some new research today that takes this all a step further.[ii]  Scientists in Ireland took a look at how different kinds of exercise impact the microbiome. They sampled feces and urine from 37 elite Irish athletes who competed in 16 different sports.  The sports were grouped by high muscle contraction/high oxygen consumption (i.e. cycling type exercise); high muscle contraction/low oxygen consumption (i.e. judo); low muscle contraction/high oxygen consumption (i.e. field hockey).[iii]

It turns out that highly dynamic (moving) forms of exercise, like field hockey, versus moderately dynamic (like fencing), versus mixed dynamic/static sports, like rowing, all lead to different microbiome profiles.  For example, high dynamic sports led to higher levels of Bifidobacterium animalis, Lactobacilllus acidophilus (25x greater than in the other groups of athletes), Prevotella intermedia, etc.  On the other hand, athletes involved in moderate dynamic sports had greater levels of Streptococcus suis and Clostridum bolteae, among others.

They also found significant differences in how the biome functions.  Middle distance running and swimming were found to have the biggest differences here.  As one example:  in the mixed high dynamic and static group (i.e. rowers), “…pathways involved with folate and amino acid biosynthesis…were found to be 1.5 times greater…” when compared to other groups.

What I found particularly interesting was that this effect was determined to be independent of foods eaten:  “The difference in  microbiomes and metabolome across groupings, in the absence of significant dietary differences, suggest a role for exercise type as a contributing factor.”

This study did not look at the reason for these differences but I will keep an eye out for future work in this field.  After all, there may very soon come a day when you can choose the probiotic that is exactly right for your sport of choice.  (2024 USA Olympic swim team, here I come!)

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[i] https://otd.harvard.edu/news/harvards-athlete-based-next-generation-probiotics-technology-licensed-to-fi/

[ii] O’Donovan CM, Madigan SM, Garcia-Perez I, et al. Distinct microbiome composition and metabolome exists across subgroups of elite Irish athletes. J Sci Med Sport. 2020; 23(1):63-8. doi: 10.1016/j.jsams.2019.08.290.

[iii] https://www.gutmicrobiotaforhealth.com/en/who-would-have-guessed-that-sport-is-impacting-our-gut-microbiota/

The Promise of Helminths for Multiple Sclerosis

Today I get to write about something other than the bacterial microbiome!  Woopa! I was very happy to find a new paper on the possibilities of using helminths (helminth immunotherapy (HIT), as these authors call it) to prevent and alleviate multiple sclerosis (MS).[i]   The article gives a great overall picture of where we currently stand, research- wise, and what work needs to be done going forward.  More than that, I also learned some new tidbits which I think are very worth sharing with you.

I’ve written before about helminths and MS.  As these authors acknowledge, what we currently know holds great hope, although it is a fraction of what we need to know.  Still, the majority of the current studies (20 of 23), “…reported a protective effect of HIT…especially when the helminth or helminth-derived product was provided prophylactically…”  Few studies currently exist on using HIT for those already affected – but I’ll come back to that in a moment as those studies too, hold promise.

One of the main issues in the field is lack of “technical” consistency.  The existing studies have used many different species of helminth and those organisms were used in many different ways.  In spite of this though, there is an overall remarkable consistency in findings.  For example, there is great consistency in all these varied experiments in the way the immune system responds to the presence of helminths:  they stimulate the Th2 family of cytokines, which includes regulatory ones, leading to lower levels of inflammation.  Another interesting, and consistent, finding has to do with the B cells of the immune system.  Generally speaking, depleting these kinds of immune cells via pharmaceutical works well for ameliorating the symptoms of MS, and thus are considered “major players in MS pathogenesis.”

Very little work (2 studies so far) has been done looking at helminths’ effects on B cells, but what we do know is that when an organism has helminths, B cells are implicated in promoting the Th2 response.  In one study, the researchers transferred B cells from helminth-infected mice with the MS-like syndrome into mice who were also afflicted, but who did not have helminths.  These B cells diminished the MS-like symptoms in the latter mice.  In a human study, B cells from helminth-infected MS patients were shown to suppress inflammatory cytokine production and to stimulate regulatory cytokines:  “Altogether, these observations suggest that HIT may modulate B cell function and contribute to the beneficial outcomes in…MS.”

Of the studies done thus far (in animal models, in which an MS-like syndrome is induced), only two have shown no protective effect from helminths.  However, results of these must be interpreted with caution.  In one of them, the helminths were cleared before MS was induced, “…which could explain the lack of an effect.”  In the other, a helminth-derived product was used – not a living organism.  The paper states that “…the majority of animal studies support the hypothesis that pre-existing helminth infection can limit the onset of MS-like symptoms in experimental models.”

The article points out that most people turn to helminths after diagnosis, and thus, studies looking at the effects helminths may have on alleviating symptoms are particularly useful.  Unfortunately, there are very few of these.  One unsuccessful one again used a product derived from Schistosoma eggs, not the actual organism.  Products derived from other helminths were more successful.  In one study, using the actual organism H. Polygyrus, partial remission was noted at only 3 weeks post inoculation.  The best human study, covering a period of 5 years, I have discussed before in that  earlier post.  Those with MS who had helminths fared way better than those without, with no worsening of symptoms or new brain lesions.

Thus far, there have been 4 human clinical trials which have reported results.  They all used Trichuris suis ova, TSO (which is a porcine-native whipworm), and varied greatly in length, from 3 to 10 months.  The only one which saw no improving trends was the 3 months one.  It appears, based upon these studies, that the longer the patient has had helminths, they better they continue to do (i.e. an uphill trend).

I feel like a broken record writing this, but we may as well get used to it because there is always more to be learned.  In this case, we really, really need more science before we know how to best to dose helminths, which ones are the best organisms (which will likely vary from disease to disease), and so forth.  Still, as this paper concludes, “…although there are only a limited number of studies that have tested whether HIT can have therapeutic effects once disease is established, there are indication of beneficial effect using some HIT regimes…”

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[i] Charabati, M, Donkers, SJ, Kirkland,  MC, Osborne, LC. A critical analysis of helminth immunotherapy in multiple sclerosis. Multiple Sclerosis Journal. 2020. doi: 10.1177/1352458519899040

Breast Cancer: A Little Bit of Yogurt Seems to Go a Long Way

This past October, I wrote about probiotic use in breast cancer.  If you remember, that paper concluded that what few in vitro and in vivo studies we have look promising.  One piece of research mentioned in that paper is particularly pertinent to today’s post:  “One Japanese study asked 306 women with BC, and 662 women without, about their diets, lifestyles and other risk factors and found that regular and long-term consumption of L. casei Shirota (found in Yakult yogurt, and which I have written about before – for example,  here ) was ‘…significantly associated with decreased BC risk in Japanese women.’”

One of the big biome stories of the week:  another paper just came out that once again, points out the fact that eating yogurt is highly associated with a decrease in breast cancer risk.[i] This paper, out of Lancaster University in the UK, suggests the following hypothesis:  “…the mechanism proposed in this article is that the bacteria which cause cancer induce inflammation which leads to the destruction of the stem cells…”  This leads to “genetic instability” and mutations within the breast cell DNA.

The authors point out that breast ducts are far from sterile.  Pregnancy and lactation are known to decrease the risk of breast cancer fairly dramatically:  “Following pregnancy and lactation, they will have a flora which is dominated by lactose fermenting bacteria.  This appears to be protective against the development of cancer.”  However, bacteria from other areas of the body, where pathogenic bacteria may be present, can travel via the blood stream and can cause dysbiosis in a wide variety of other tissues.  For example, periodontitis, which is inflammation of the gums caused by bad bacteria, is highly associated with a wide variety of other illnesses including senility, atherosclerosis, rheumatoid arthritis and cancer (including of the gastrointestinal tract, breast, prostate and pancreas).  It is likely that “…organisms of the mouth are carried through the blood to distant sites and cause direct tissue destruction and inflammation.  In the breast we envisage that the pathogenic bacteria directly damage epithelial cells…”

The good news:  eating daily yogurt seems to make a very statistically significant difference in breast cancer risk.  One meta-analysis (which has been replicated), which looked at thousands and thousands of cases, showed that “…high and modest dairy consumption significantly reduce the risk of breast cancer compared with low diary consumption.”  Further analysis showed that the effect forms of dairy were low fat dairy and yogurt – not other forms, like fluid milk.  And the amount:  about 2-3 cups of these forms of dairy per day (400-600 grams).

In a press release about the study, one of the authors states, “…The stem cells which divide to replenish the lining of the breast ducts are influenced by the microflora, and certain components of the microflora have been shown in other organs, such as the colon and stomach, to increase the risk of cancer development. Therefore, a similar scenario is likely to be occurring in the breast, whereby resident microflora impact on stem cell division and influence cancer risk.”[ii]

The conclusion:  “…there is a simple, inexpensive potential preventive remedy; which is for women to consume natural yogurt on a daily basis…”

A little bit of good news, on the things-you-can-do-now front!

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[i] Marwaha, AK, Morris, JA, Rigby, RJ. Hypothesis: bacterial induced inflammation disrupts the orderly progression of the stem cell hierarchy and has a role in the pathogenesis of breast cancer. Medical Hypothesis. 2020; 136:109530. doi:10.1016/j.mehy.2019.109530.

[ii] https://medicalnewsbulletin.com/can-eating-yogurt-prevent-breast-cancer/

Fiber: And You Thought This Was Simple (ha!)

Many times over the years I’ve written about prebiotic fibers and gut health.  What seems so simple at first glance (i.e. “eat more fiber”) turns out to be anything but…just like everything else having to do with the gut biome!  I just finished reading a really interesting little article that was published in the proceedings of the Nutrition Society, from a conference held at the Royal Society of Medicine in the UK.[i]  It is a great follow up to my post of a few weeks ago, which talked about how too much of a good thing is just as bad as too little.  (As my old mentor, Dr. Sidney Baker, used to say (summarizing basically all of medicine):  does this patient have too much of something or too little?)

Dr. Rhodes summarizes some recent work looking at dietary fibers and to summarize in just a few words – they are not all the same. Historically, starting in the 1990s or so, we were all told to get at least 5 servings per day of fruit and vegetables, excluding starchy vegetables like potatoes, yams and plantains which didn’t “count.”  This, according to Dr. Rhodes, had very little evidence supporting it and in fact, there is “…some evidence that plantains for example might be particularly beneficial.”

The research on simply adding more fiber to the diet to stave off colorectal cancer has been contradictory at best.  Dr. Rhodes suggests that this might be an issue of over generalization:  “One possible conclusion from these contradictions is that it may not be helpful to generalize about health impacts of large food groups.” After all, fruit and vegetables, for example, contain many, many different nutritional components and too much of one or too little of another can have major health implications.

Looking then at colorectal cancer as an example, he points out that bacteria of the gut has come under great suspicion as playing a major role in its development:  “…cancer is so relatively rare in the small intestine (.4% life-time incidence) compared with the colon and rectum (6% life-time incidence in western countries) and bacteria re approximately 104 more numerous in the colon.” Research has shown some highly suspect bacteria include Fusobacterium and E. coli, among others.  E. coli has been found to adhere to the mucosal lining of the gut in both colon cancer and in Crohn’s disease, and promotes inflammation. In places where the diet includes high amounts of fiber (I’ve written about this before here), colon cancer and inflammatory bowel diseases are extremely rare.  Therefore, “…we investigated the possibility that soluble dietary fibres and other complex carbohydrates might be able to inhibit E. coli adherence to the epithelium.”  It turned out that fiber from plantains and broccoli, but not from apples or leeks, have a profoundly positive effect on protecting these bacteria from invading the mucosal lining.  And this applied to not just E.coli, but also other pathogenic bacteria including C. difficile.  Dr. Rhodes calls these inhibitory fibers contrabiotics.

You’ll remember that  bacteria eat these fibers and in fermenting them, produce short chain fatty acids (SCFA).  SCFAs are very, very beneficial to health, generally speaking, as you know, but…as I mentioned in the first paragraph of this post, too much of anything is NOT GOOD.  Studies on different soluble fibers have shown that higher doses of citrus pectin tend to be beneficial whereas inulin may be harmful.   Animal studies have shown that in mice in whom the anti-inflammatory cytokine, IL-10, is blocked, inducing inflammatory bowel disease, a diet rich in citrus peel pectin ameliorated the disease whereas a diet containing a similar amount of inulin exacerbated the colitis.

Why?  Inulin was correlated with high amounts of the short chain fatty acid, butyrate.  Now, butyrate, of course, is usually very good.  But that is the key phrase – in the right amount:  “Although butyrate is widely regarded as beneficial to the colonic epithelium, it is perhaps insufficiently recognized that this benefit is very much dose-related.”  Remember my article on propionic acid where I talked about research stating exactly the same thing?  High doses of butyrate, “…have been known for a long time to be toxic to colon epithelial cells in vitro…”

The ecosystem of the biome is unbelievably convoluted and science has barely begun to pick apart how each element affects others.  There are trillions of organisms interacting with each other, secreting an unbelievable array of metabolites (most of which are still unknown).  Throw food into the mix and – well, I reckon it will be decades and decades before we have even an inkling of how this all works. The question of fiber alone is not even vaguely simple:  “The impacts of fibre on microbiota are complex and also depend on the existing microbiota.”

Dr. Rhodes mentions other components of fruit and vegetables (like lectins – which I may write about soon) and also briefly addresses the question of emulsifiers in processed foods.  To summarize the latter: they are bad.  I’ve written about this before (just one example of several – here) so I won’t go into any detail now.  Just avoid them as much as you can.

So to conclude, two major points from this article:

  1. Some sound advice: “Dietary advice to the general public should therefore address factors that reduce the risk of a range of conditions, not just one, and should ideally impact beneficially on all-cause mortality….There is, for example, evidence that adherence to a Mediterranean diet, and its components; low meat, high fruit and vegetable, nuts, and olive oil impacts beneficially on all-cause mortality.”
  2. “If you are searching for a single dietary component that might prolong life there is arguably nothing that has a stronger case. Regular coffee drinking has been associated with reduced risk of type 2 diabetes, cardiovascular mortality, cancer, cirrhosis and most importantly, with a reduction in all-cause mortality.”

Waahooo! (Judy wrote, swallowing another mouthful of java…)

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[i] Rhodes, J.M. Conference on ‘Diet and Digestive Disease’ Plenary Lecture 1: Nutrition and gut health: the impact of specific dietary components – it’s not just five-a-day.  Proceedings of the Nutrition Society. 2019.  doi:10.1017/S0029665120000026

Another Step Forward: Ankylosing Spondylitis and the Microbiome

The evidence continues to mount pointing to microbiome alterations as being (one of?) the underlying cause of ankylosing spondylitis (AS).  Just a few weeks ago, I wrote about a long-term study on 150 patients with AS which showed distinct alterations in the biome.  A second major paper (out of China) appeared in the Journal of Autoimmunity within the last few weeks which moved the research forward once again.[i]

I’ve pointed out in previous posts about AS that “…at least 2.7 MILLION people suffer from these diseases in the USA alone, which is almost 3X the number of people that suffer from the way better known Parkinson’s disease alone…”  This is an illness that affects millions of people at yet, remains relatively unknown and unstudied.  Worse still, it typically takes years to be diagnosed, leaving many people untreated and suffering.  I am always really happy when I see some new information about it.

In this recent paper, the scientists looked at the fecal microbiome of 108 people with AS, 85 of whom were untreated, the other 23 of whom were undergoing treatment.  They also had feces from 62 healthy controls.

They did multiple tests which provided a great deal of new data:

  1.  They confirmed that specific bacterial species are at higher levels in those with untreated AS when compared to healthy controls.  These species include Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri.  Levels of other bacteria were lower than controls, including Enterococcus faecium.
  2. When patients with AS are treated, levels of some bacteria began to resemble those of healthy controls: Prevotella levels decreased and Enterococcus faecium increased:  “…the facts  above indicate a possible causal relationship between Prevotella copri and AS pathogenesis.”  The shift in this bacterial species toward control levels was more marked with immune-suppressant medicines than with just NSAIDS (non-steroidal anti-inflammatories, like ibuprofen).
  3. Several pathways associated with the microbiome are altered in those with AS, including one that may lead to bone destruction and compromise gut wall integrity.
  4. The pattern of bacterial alterations in those with AS is distinct enough that it looks like it will be able to be used diagnostically. This is really good news, in that, as mentioned above, diagnosis of the condition typically takes YEARS, leaving people untreated, or inappropriately treated, which of course leads to further bone deterioration.
  5. A quick definition for anyone unfamiliar:  molecular mimicry encompasses the idea that foreign proteins may look an awful lot like our bodies’ own and thus, we form autoantibodies to both, leading to autoimmune disease.  These researchers found 3 peptides (which are just short proteins) “…among bacterial species enriched in AS patients that are similar to auto-antigens with a known role in AS.”  In fact, one of these peptides “…stimulated secretion of the pro-inflammatory molecule IFN-gamma by immune cells in AS patients, but not in controls.”[ii]  This peptide mimics one found in collagen, which is the main component of cartilage.  As the body attempts to destroy the foreign invader, it ends up attacking its own cartilage.

The conclusion remains that “Despite the fact that several gut microbiota studies have been performed in AS patients, we are still far from a clear causality between gut dysbiosis and AS pathogenesis. Unlike other inflammatory diseases such as RA whose development have been proven to partially attribute to gut dysbiosis, the exact relationship between any specific microbial taxa and AS pathogenesis has not been reported yet.”  So way more still needs to be done.

Still, this year already we’ve seen two major steps forward in research.  And that is, at least, of some comfort.

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[i] Zhou, C, et. al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis. Journal of Autoimmunity. 2019. DOI: 10.1016/j.jaut.2019.102360

[ii] https://ankylosingspondylitisnews.com/2020/01/23/gut-microbiome-in-ankylosing-spondylitis-patients-is-imbalanced-and-contributes-to-inflammation/