Missing Microbes May Explain Limited Responses to Transitioning to a Whole Food Plant Based (WFPB) Diet

Missing Microbes May Explain Limited Responses to Transitioning to a Whole Food Plant Based (WFPB) Diet

Lifestyle medical doctors, such as Ron Weiss and Zach Bush, strongly promote WFPB diets to their patients and often see amazing results. However they and other plant-based medical doctors admit that the degree to which WFPB diets benefit their patients can vary greatly.

Results range from patients who experience tremendously improved health in a short time period, to patients who experience limited health improvements, even when fully compliant for many months.

Individual Variability

Although we all belong to the same species, each of us is a unique individual. How well we respond to a WFPB diet depends on countless variables including genetic differences, medical conditions, the amount and type of damage to organs and metabolic systems, medications, and physical limitations.  But the unique makeup of our gut microbiome may be the most important factor of all. The gut microbiome is a community of tiny organisms in our intestines that plays a central role in our health.  It is involved in many physical processes, like digestion, nutrient absorption and immune response. For more general information about the gut microbiome, check out this earlier article.  As mentioned in the article, people eating plant-based diets have been shown to have healthier microbiomes than people eating animal based diets. Researchers know that the diversity of the gut microbiome increases when someone transitions from a western-style diet to a WFPB diet.  It can happen quickly. But for some transitioners, the increased diversity of intestinal microorganisms may be missing some important types or strains of microorganisms which may prevent drastic health improvement that is often experienced by others.

Missing Microbes, by Martin J. Blaser MD

Martin J. Blaser MD is the director of the Human Microbiome Program at NYU and he has studied the role of bacteria in human disease for over 30 years.

In his book, Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, Blaser argues that while antibiotics have saved countless lives, they’re an assault on our microbiome. His experiments have linked extinctions of certain microbes to disorders such as asthma, allergies, diabetes, obesity and even some forms of cancer. The problem is due in part to the overuse of antibiotics, Caesarian section deliveries, and modern sanitation.

Overuse of Antibiotics and Super Bugs

Most of us have heard that the overuse of antibiotics has resulted in the development of super-resistant bugs.  More and more bugs are developing resistance to the most commonly prescribed antibiotics.

According to the U.S. Centers for Disease Control and Prevention (CDC). drug-resistant bacteria infect more than 2 million people nationwide and kill at least 23,000 every year.

Antibiotics are effective against bacterial infections.  They are also given to livestock to promote growth. But antibiotics don’t work at all on viruses, such as those that cause colds or flu.

Many antibiotics prescribed for people and animals are unnecessary and this unnecessary usage is causing the Super Bug crisis.

Dr. Dennis Nixon, a National Institutes of Health (NIH) expert in bacterial and fungal diseases states; “bacterial infections that were treatable for decades are no longer responding to antibiotics, even the newer ones,”

Dr. Jane Knisely, who oversees studies of drug-resistant bacteria at NIH, states: “We need to make the best use of the drugs we have, as there aren’t many in the antibiotic development pipeline”.

This explains why many pediatricians delay prescribing antibiotics in certain situations for ear infections because often the infections resolve on their own without the use of antibiotics.  Some research now shows that antibiotics are less effective than previously thought for a very common type of sinus infection.  Future such research will help doctors determine when antibiotics are appropriate and when they are not.

Unintended Consequence of Overusing Antibiotics = Missing Microbes

“Some bacteria are indisputably bad. But others boost our immunity, protect us from infection and produce the enzymes we need to digest our food. Without these bacteria, we wouldn’t survive, says Dr. Blaser.

In addition to the development and spreading of life-threatening super bugs, the overuse of antibiotics and, to a lesser extent, the increasing amount of Caesarian-Section deliveries and modern sanitation, appear to be causing the extinction of beneficial microbes.  Dr. Blaser believes that microbe extinction may be at the root of modern plagues like asthma, allergies, diabetes, obesity and even some forms of cancer.

The Fascinating Story Of Helicobacter Pylori (H. pylori)

Helicobacter pylori (H. pylori) has been called the “poster child for microbial extinction.” It was originally known for causing ulcers at a time when doctors believed no bacteria could survive the stomach’s acidic environment. In fact, Dr. Barry Marshall, who discovered the bacteria, drank a vial of the stuff, and within weeks, developed stomach pains and gastritis, precursors to the stomach ulcer. Marshall and colleague Robin Warren earned the Nobel Prize in 2005 for their research.

Because of Dr. Marshall’s research, Dr. Blaser initially thought that H. pylori was bad. But his research showed just the opposite. This microbe, he found, was interacting with the immune cells that line our stomach. And losing it appeared linked to several immune and metabolic disorders: asthma, allergies, celiac disease, even acid reflux disease.

1. pylori, like much of our microbiome, is acquired early in life. “Contrary to popular belief, babies are not born sterile”, said Maria Gloria Dominguez-Bello, associate professor of medicine at NYU.

In the early 20th century, most Americans had H. pylori in their stomachs. Fast forward to present day, and fewer than 6% of American children born after 1995 have it. These trends are the same in Australia, Germany, the Netherlands and Scandinavia.

We have been slowly eradicating H. pylori with antibiotics — the organisms have become quite uncommon in developed countries.

But as they vanish, Dr. Blaser notes, a small epidemic of esophageal disease follows, with inflammation causing heartburn and even cancer. It turns out that this bad germ is also good, instrumental in protecting the human esophagus from trouble.

Dr. Blaser states: “One day it occurred to me that this is an ancestral organism that’s disappeared. But ancestral organisms aren’t supposed to disappear. If one guy is disappearing, maybe some others are disappearing.”

Bombarded by Antibiotics

According to Blaser, 258 million courses of antibiotics were prescribed in the United States in 2010. On average, American children receive three courses of antibiotics before their second birthday. What type of havoc is this wrecking on their microbiomes? How is this affecting their immune systems and various metabolic pathways?  Research is underway that will eventually begin to answer these questions. In the meantime, Blaser argues, we urgently need to reconsider the idea that taking antibiotics has no cost, and take them only when absolutely necessary.

 Caesarian Sections

Babies who are born by cesarean and never make that trip through the birth canal apparently never receive some key bugs from their mothers — possibly including those that help to maintain a healthy body weight. Children born by C-section are more likely to be obese in later life.  C-Section birth has also been associated with the later development of asthma, allergies and type 1 diabetes.

A study by Bokulich et al. (2016) investigated the impact of delivery modes (C-section and vaginal birth) on microbial maturation and diversity during the first two years of a child’s life.  The study profiles microbial development during the first two years of life in 43 infants. Bokulich et al. (2016) found that C-section delivered infants had altered intestinal bacterial richness and very different microbial diversity compared to vaginally born infants throughout the first two years of life. Abundances of multiple bacterial species were altered, and it was noted that Bacteroides abundance was significantly lower in infants delivered by C-section.  Bacteroides and other bacteria help aid in digestion and nutrient absorption, so it is important to have a strong foundation of these bacteria in infants, which does not seem to be the case for C-section infants.  Additionally, more beneficial bacteria in the gut protect the host from invasion by negative species

Bokulich et al. (2016) also found that after one year, the child’s balance of Bacteroides, Bifidobacterium, and Enterobacteriaceae, three bacterial species that dominated the gastrointestinal tract during the first year of life, had been replaced. In infants delivered by C-section, there was significantly more Lostridiales and Enterobacteriaceae during the first year, filling the void left by Bacteroidales.  More research has to be done to fully understand the impact this may have on the infants later in life.

Can anything be done for C-Section Babies?

Because the rate of C-sections is increasing in the United States and other countries, Dominguez-Bello et al., 2016 aimed to test if they could alter the microbiota of C-section delivered infants to be similar to vaginally born.  Through this, the researchers hope to see if maybe they could prevent the development of disease later on.

Although it was a smaller study, it showed that the microbiota of C-section babies could be partially restored through the method of vaginal swabbing.  Longer studies would have to be done in order to determine if this impacted the infants later in life, such as avoiding some of the diseases associated with C-sections listed above.  Also, different methods of exposure to the microbiota could be tested to see if there was an impact, because different areas of the infant were more susceptible to the exposure than others.  The researchers hope that another study could be done to expose the infants to the microbiota for a longer period of time, which would more closely resemble the exposure during vaginal birth.

What about Hand Sanitizers?

Here are some thoughts from Dr. Blaser:

“I have a small photo gallery: When I see a hand sanitizer in a new place I take a picture of it. They’re very important in hospitals, but what’s the rationale for hand sanitizers everywhere? They don’t have antibiotics in them, but they have antibacterials like triclosan. Triclosan is in our soaps and our deodorants, in our clothes, in our pizza cutters, in our staplers. It’s everywhere. This is a germ phobia that is unsupported.”

Probiotics

Per Dr. Blaser –

“In general they’re safe—they don’t seem to be associated with health problems. But with few exceptions, they haven’t been tested in rigorous clinical studies. The future will hold a lot of probiotics, but we’re going to have to discover what their specific activities are and when we need to use them. Maybe there will be particu­lar bacteria that are good to give to kids with asthma. Maybe if there’s one that turns off Th1 immune cells, that will be a good probiotic for people with rheuma­toid arthritis. I think we’ll be able to harness these microbes, just as we’ve har­nessed the microbes that make bread and beer for us.”

Here are some thoughts from Dr. Zach Bush:

“There are a lot of people out there taking a lot of probiotics! That’s why probiotics are now a $30 billion global industry, with over 180 products on the market. In general, that’s a promising sign, indicating that doctors and patients really are thinking beyond the pharmaceutical options when it comes to managing digestive system problems and other chronic disorders. But like so many things in life, it’s really easy to overdo it with probiotics. The more we learn about the gut microbiome, the more I think we need to check our zeal for probiotics. To be sure, probiotics can be a valuable tool in the context of a comprehensive treatment approach, but as with any other tool, excessive or inappropriate use can be problematic.”

Dr. Bush states that it is estimated that the optimal healthy human gut should contain between 20,000 and 30,000 different species of bacteria. The greater the diversity, the healthier the microbiome.

Dr. Bush’s major concern is with the current approach to probiotic use. He states that it is doing on a microscopic level what crop monoculture is doing in agriculture; favoring a relatively small number of species at the expense of ecosystem diversity.

A typical probiotic supplement delivers 35 billion to 50 billion CFUs of just a few species. While some products contain up to 24 species of bacteria, that’s still a far cry from the diversity that we know to be optimally healthy. Giving 35 billion copies of the same bacteria over and over again in the gut is absolutely creating monoculture. You might call them “good bacteria,” but if you’re using them chronically, you could create real problems.

Here is Dr. Bush’s explanation of why probiotics often only help in the short term and may be harmful taken in the long term.:

“As functional medicine doctors, a whole group of us jumped on, 10 or 15 years ago, and said gut health is important; we said probiotics are critical, and every patient needs to be on a probiotic regimen.

Many physicians and their patients became enamored of probiotics because they recall those first two weeks of first being on a probiotic. Most of these patients were recovering from gastroenteritis or from antibiotic exposure, chronic fatigue, whatever it was. Their physician finally recommended a probiotic, and they finally felt some improvement. They were like, “Okay, that’s a good edge off my pain or suffering” or whatever it is, my irritable bowel syndrome.

They get stuck in the mentality of, “I remember I was worse, then I started this and I was better,” so they assume that if they stop that they’re going to get worse again.”

Many of our patients really do feel better in the first couple of weeks on probiotics, even if they have gut overgrowth of invasive species like E. coli. When you take a probiotic and overwhelm that biome with seven species that are good, you’re going to feel better, but then you will plateau.

In people with longstanding digestive system disorders, the benefit obtained from probiotics can only really occur for those first couple of weeks.

Thereafter, the chance of actually obtaining long-term symptomatic relief is almost zero.

I don’t see probiotics being helpful at all in the long-term management of a patient.  If I see a patient who’s coming to the clinic and they’ve been on chronic probiotics, I generally stop them cold turkey.

What I’m saying is, we need to stop trying to micromanage the gut.

At our clinic, we always stop probiotics after one to two weeks. The only time we use them clinically now is if there’s been exposure to antibiotics or to a chemotherapy agent, or occasionally if there’s a severe gastroenteritis or viral infection”.

What Should Be the Goals of Microbiome Research?

According to Dr. Blaser, these should be goals of microbiome research:

• Develop better diagnostics that can identify specific microorganisms that are causing symptoms
• Develop narrower antibiotics that kill problematic microbes and leave beneficial microbes unscathed
• Develop diagnostics that can identify microbes that are missing from a dysbiotic gut
• Develop procedures to insert missing microbes into a dysbiotic gut.

Pushback against Some of Dr. Blaser’s Views

It’s important to remember that the study of the human microbiome is in its infancy. We have an enormous amount to learn.  Because of this, some experts believe Blaser and his colleagues are jumping the gun with some of their conclusions about the long term effects of overusing antibiotics.

One such expert is Jonathan Eisen, an evolutionary biologist and professor at U. C. Davis.  Professor Eisen believes that Dr. Blaser and his colleagues are overselling the long term effects of overusing antibiotics.

He takes particular umbrage against Dr. Blaser’s statement that “antibiotics are extinguishing our microbiome and changing human development”.

Here are Eisen’s thoughts about that statement:

“Extinguishing our microbiome?  Really?  The evidence simply does not support such a claim.  I personally think antibiotics may be contributing to messing up the microbiome in many people and that this in turn might be contributing to the increase in a variety of human ailments (e.g., I mentioned this issue in my TED talk and many many times here and elsewhere).  But “extinguishing”?  Not even close.  In fact, many of the published studies done so far suggest that the human microbiome is pretty resilient in response to antibiotics.  Really serious overselling of the impact of antibiotics by Blaser. And “changing human development?”  Not sure what the evidence for that is either.  Most likely this refers to the role the microbiome plays in immune system development, but I am not aware of strong evidence that antibiotics lead to changes in human development.”
Professor Eisen also takes issue with Blaser’s belief that microbe extinction may be the root of modern plagues like asthma, allergies, obesity and even some forms of cancer.

Here is Eisen’s response:

“What?  Now antibiotics cause obesity?  And allergies?  And cancer? Sure – there is good reason to think that antibiotic usage plays a role in obesity and allergies.  The evidence is not yet completely overwhelming, but it is certainly a reasonable notion.  But how did cancer get thrown in here?”
Professor Eisen makes clear that he thinks that the microbiome is critical to many human functions and that screwing with it via excessive use of antibiotics seems like a very, very bad idea. But he asks: “Do we really need to overstate what we know in order to effect change?  Do we need to say things like “antibiotics are extinguishing our microbiome” which is simply untrue? “   Eisen doesn’t think so.  He considers such statements as examples of misleading the public and that people would take notice of Dr. Blaser’s research without these misleading statements.

Future Microbiome Research

Eisen is hardly alone when it comes to providing backlash to microbiologists who make claims about the potential health benefits of gut microbiome research.

In an excellent article entitled “I Had The Bacteria In My Gut Analyzed. And This May Be The Future of Medicine”, Paul O’Toole, a professor at the Alimentary Pharmabiotic Centre, in Cork, Ireland gives his explanation of this backlash.

O’Toole admits that the connections between the microbiota and many diseases are inconclusive and highly speculative.

The problem, he says, is that microbiologists have been very good at discovering gut bacteria and identifying what roles they might play, but they have been slow to develop mechanisms to establish firm causal links and practical applications.

He states: “I personally hope it doesn’t become the solution for everything because it’s not going to be credible, it’s simply not true. There’s plenty of evidence that most human major diseases have a physiological or lifestyle basis, but it’s probable in some of those that the gut microbiota is a modulating factor that contributes to the overall risk.”

O’Toole is interested in further study of the gut microbiome in the elderly. He explains that significant links have been established between gut microbiota and inflammation, sarcopenia and cognitive function.

Inflammation

“Inflammation,” he says, “is not a swollen thumb. Inflammation means how activated your immune system is.   In old people, the immune system is typically turned on and that’s not good, because if it’s turned on, when they get a winter flu all their energies are expended chasing ghosts. So you want to turn down the inflammation.”

Sarcopenia

Sarcopenia means loss of muscle mass. It happens as we get older because the body becomes less efficient at turning protein into muscle which is why older people need to have more protein. “We think that the narrowing of gut bacteria in old people is making the intestine less efficient at absorbing proteins,” says O’Toole.

Cognitive Function

Cognitive function is partly related to what’s known as the brain-gut axis. As all those phrases like “gut wrenching” and “gut feeling” suggest, there is indeed an intimate link between the brain and the gut. Our intestines are acutely responsive to shifts in our emotions and mental states. But it’s a two-way street: studies suggest that our brains and emotions are also sensitive to what’s going on in our guts.

Typically, cognitive function is only slowly diminished as we get older, but in some cases it can quickly accelerate.

There are physiological reasons like Alzheimer’s and senile dementia that explain rapid cognitive impairment,” O’Toole says. “But the rate of loss could also be affected by compounds made by bacteria, and that’s what we’re targeting. Bacteria produce chemicals which are analogues – in other words they look identical to normal human transmitters. What we hope is that we can improve the ability of old people to process data.”

Common to all these issues, particularly among the aged, is the narrowing of the gut microbiota which, in turn, is usually the result of a narrowing of diet. This is a point that O’Toole repeatedly emphasizes.

“Diversity is the key. What we see with people on narrow diversity diets is that the microbiota collapses. A good analogy would be an ecosystem like a rainforest, where you’ve got loads of plants and animals interacting. It’s evolved over tens of thousands of years, then one of the key species, a tree, gets cut down and you get ecological collapse.

“And if you had a gentleman whose wife died and she had done all the cooking, and then he’s suddenly eating toast and marmalade, the diversity of gut microbiota will collapse – because diversity of diet correlates with diversity of microbiota – and you will get a range of health problems associated with that.”

Can Missing Microbes Be Replaced

Right now, O’Toole would like to like to reduce the lower diversity microbiota in the elderly by means of dietary supplements. “But we worry that, as the World Wildlife Fund says, extinction may be forever. That if a particularly good bacterium is missing from an elderly person, we may not be able to get it back by diet alone.”

The solution in that case might be fecal microbiota transplantation, which O’Toole helpfully clarifies, “is the idea of transplanting someone else’s poo into a recipient”.

O’toole acknowledges that the thought of this procedure makes many people feel queasy.

But it’s already happening in North America and O’Toole suggests that such transplants may help prevent ulceration of the colon – a condition that nearly killed his father.  In fact, it is now recommended by the Infectious Diseases Society of America (IDSA) as a treatment for recurrent cases of Clostridium Difficile infection, often called C. diff. C. diff is an opportunistic pathogen, invading the gut after antibiotics have wiped out the healthy bacteria that populate the gastrointestinal tract. The illness is most dangerous for people who are older than 65 or whose immune systems are weak. An estimated 15,000 to 30,000 Americans die from it each year, and treatment costs run to more than $4.8 billion. The success rates for fecal transplants for C. diff approach 90%.

My Thoughts

In a recent interview,  Lifestyle Medical MD Ron Weiss stated that he suspects that his patients that experience a limited or small response to transitioning to a WFPB diet, may be missing important ancestral microbes.  And these may be microbes that haven’t even been discovered yet.  If Dr. Weiss is correct, then Dr. Blaser’s research goal of developing diagnostics that can identify missing microbes is worthy of our attention.

The synergistic effect that nutrition has on our health can probably be partly explained by the gut microorganisms that thrive on a particular diet. Considering that we have trillions of microorganisms comprised of thousands of different species in constant interaction with our gut and each other, it seems that teasing out the effects of specific species will be an amazingly daunting task for researchers.  So we probably shouldn’t hold our breath waiting for such breakthroughs.

Based on our current knowledge it seems that the best way to maintain a diverse, healthy gut microbiome, is to consume a diverse whole food plant based diet.

Maybe someday, as the study of the gut microbiome advances, dietitians will be able to provide far more personalized advice to clients. It will be interesting to see what future research teaches us.

Stay Healthy and Strong!