Breast Cancer Basics: Prebiotics and Probiotics

What is the Microbiome?

Did you know that there are 10-times more microbes on and in the human body than there are human cells? We call the collection of these microbes our “microbiome.” The majority of these microbes (which weigh as much as 5 pounds) live in our intestines and are comprised of many different types of bacteria, fungi, protozoa and viruses.

Research into the human microbiome has exploded in recent years amid growing understanding of the impact these organisms have on our health. In fact, the microbiome was not generalized recognized to exist until the late 1990s.

What are Probiotics?

The International Scientific Association for Probiotics and Prebiotics defines “probiotics” as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” (REF) These microorganisms, which consist mainly of bacteria but also include yeasts, are naturally present in fermented foods, may be added to other food products, and are available as dietary supplements.

Impact of the Microbiome on our Health:

The activity and composition of these microorganisms (collectively known as the gut microbiota, microbiome, or intestinal microflora) can affect human health and disease. The bacteria in the microbiome help digest our food, regulate our immune system, protect against other microbes that cause disease (i.e. Clostridium difficile, Candidiasis), produce vitamins (i.e. B12, thiamine, riboflavin, K), detoxify and eliminate chemicals and carcinogens, maintain a healthy intestinal lining. Dysfunction of the microbiome (often referred to as “dysbiosis”) has been linked to an increasing number of health conditions, such as:

• Insulin resistance and type 2 diabetes
• Obesity
• Rheumatoid arthritis
• Ankylosing spondylitis
• Psoriasis
• Muscular dystrophy
• Multiple sclerosis
• Neurogenerative diseases
• Celiac disease
• Fibromyalgia
• Cancer
• Mental and cognitive health
• Cardiovascular disease and high blood pressure
• Inflammatory bowel diseases and irritable bowel syndrome
• Aiding digestion
• Allergies
• Increased susceptibility to infectious diseases
• Decreased effectiveness of immunotherapies and chemotherapy drugs

How does Dysbiosis Develop?

Just as in gangland movies, when the good guys are killed, the bad guys take over. This takeover by the “bad” microbes is most often a silent shift (asymptomatic), so you will likely have no way of knowing it is going on. Many things can kill off our “good” microbes (or cause an overgrowth of the bad bacteria), such as:

• Chronic stress
• Not getting enough sleep or quality sleep
• Not consuming enough fiber or “prebiotic” foods (see below)
• Consuming large amounts of high-glycemic carbohydrates
• Taking certain medications (i.e. antibiotics, immunotherapies, chemotherapy, steroids, non-steroidal anti-inflammatories, acid blocking proton pump inhibitors, etc.)
• Food sensitivities or allergies
• High salt diet
• Fried foods
• Excessive alcohol consumption
• Smoking
• Toxins, pesticides and certain preservatives (i.e. polysorbate 80 and carboxymethylcellulose) in food and water
• Not getting enough physical activity
• Lack of dietary variety
• Constant caloric intake (certain bacteria thrive in a calorie dense environment, while other thrive in a calorie scare environment; consider episodic fasting)

What are Prebiotics?

“Prebiotics” should not be confused with “probiotics.” Prebiotics are a special type of fiber that pass through the stomach and feed the good bacteria that live in your large intestine. Dietary fibers are carbohydrates with both soluble and insoluble parts. Insoluble fiber is resistant to digestion. Insoluble fiber has many benefits, including preventing constipation and possibly reducing the risk of diverticular disease. Soluble fibers can be broken down by bacteria in the gut to produce active byproducts such as short-chain fatty acids, which are associated with the health benefits linked to fiber.

Short-chain fatty acids (SCFAs) are major end products of bacterial fermentation in the colon and are known to have wide-ranging impacts on health (REF). Butyrate in particular is important for maintaining health via:

• regulation of the immune system
• maintenance of the epithelial barrier
• promotion of satiety following meals
• protection against colorectal cancer, inflammatory bowel disease, graft-versus-host disease, diabetes, and obesity

There are three criteria for classifying a compound as prebiotic:

1. It is resistant to stomach acid, digestive enzymes and is not absorbed in the gastrointestinal tract
2. It is fermented by intestinal bacteria
3. It selectively promotes the growth of intestinal bacteria associated with health and well-being

Many fiber components meet these requirements, but not all. Examples of prebiotics:

• Inulin (Fructo-oligosaccharide, FOS)
• Galactose (Galacto-oligosaccharide, GOS)
• Glucose (Isomalto-oligosaccharide)
• Fructose (Lactulose)
• Xylose (Xylo-oligosaccharide, XOS)
• Arabinose (AX)

Prebiotic fiber is found in many fruits and vegetables such as:

The Institute of Medicine currently recommends an average of 25 grams of fiber per day for women and 38 grams per day for men. However, the average American consumes just 15 grams per day.

https://youtu.be/0z47wLZ4-O4

It’s not easy to get enough prebiotic fiber from all these different foods, as they contain relatively small amounts of prebiotics per serving. The most studied of these prebiotics is Inulin (FOS), and it’s ability to stimulate healthy bacteria and butyrate production is well documented. Dr. Lawenda often recommends that his patients focus on getting enough fiber per day rather than worrying about getting enough inulin. However, for those who don’t want to consume lots of fiber-rich plants each day, he recommends that they consider taking inulin as a supplement. Based on research, 5 grams of inulin a day boosts the growth of the good probiotic Bifidobacteria in your gut. Eight grams or more per day helps increase calcium absorption. Getting 12 grams of inulin a day has been shown to help promote regular bowel movements. (REF) The amount of inulin that’s tolerated (side effects: bloating, cramping, loose stools) seems to vary from person to person. Most people do well with up to 10 grams of inulin and 5 grams of FOS a day. This is Dr. Lawenda’s favorite inulin supplement (Bulk Supplements)

Prebiotics Can Cause Problems for Those with FODMAP and Lectin Sensitivities:

One of the most common causes of intestinal inflammation is irritable bowel syndrome (IBS), affecting 10% of adults in the U.S. Since inflammation in the gut can cause systemic inflammation (a key driver of cancer), it’s one of the important factors I evaluate in my patients. IBS symptoms may include: —cramping —diarrhea —constipation —gas —bloating What Are FODMAPs? FODMAP stands for “Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols. These fermentable short-chain carbohydrates are prevalent in the diet. —Oligosaccharides: fructans and galacto-oligosaccharides (GOS) —Disaccharides: lactose —Monosaccharides: fructose —Polyols: sorbitol and mannitol Researchers discovered that the small intestine does not absorb FODMAPs very well. They increase the amount of fluid in the bowel. They also create more gas. That’s because they are easily fermented by gut bacteria. The increased fluid and gas in the bowel leads to bloating and changes in the speed with which food is digested. This results in gas, pain and diarrhea. Eating less of these types of carbohydrates should decrease these symptoms. Many of the foods that are excluded in the are those that also contain lectins, so following a low FODMAP diet will often address both concerns. (Read more about the “Low FODMAP Diet“). Lectins are sugar binding proteins that are commonly found in a variety of foods such as cereals, fruit, vegetables, animal products and fish. Most of the research on the results of consuming lectins is confined to the effect of plant lectins on animals where, for instance, they can survive transit through the gut and have a variety of gastrointestinal and systemic effects. These studies have shown that lectins can interfere with absorption of nutrients with these effects sometimes being called “anti-nutritional.” There is also evidence that some lectins may affect the gut microbiome as well as having systemic effects such as the modulation of inflammation and immune function. (REF) Foods highest in lectin include:

• Nightshade vegetables, such as tomatoes, potatoes, goji berries, peppers, and eggplant
• All legumes, such as lentils, beans, peanuts, and chickpeas
• Peanut-based products, such as peanut butter and peanut oil
• All grains and products made with grain or flour, including cakes, crackers, and bread
• Many dairy products, such as milk

Lab Testing for FODMAP and Lectin Food Intolerances:

I often recommend that patients try an elimination-reintroduction diet to try to figure out how they feel when they remove certain foods from their diet. If they are very symptomatic after consuming FODMAP or lectin-rich foods, this approach can be quite informative and therapeutic. However, food sensitivities may be more subtle and hard to identify, yet still be a source of gut inflammation and leaky gut. This situation can be identified with elevated inflammatory (calprotectin) and leaky gut (zonulin) proteins detected on stool testing (i.e. GI-MAP assay), without necessarily causing dysbiosis (at least, early on in this process). To help try to identify these more subtle food sensitivities, I run a high quality IgG and IgA food intolerance test (my favorite is the Cyrex 10 Multiple Food Immune Reactivity Screen™), which simultaneously assesses immune reactions to foods, raw and/or modified, food enzymes, lectins and artificial food additives, including meat glue, colorings and gums. I will then have the patient remove those foods that are positive from their diet and help them address any co-existing dysbiosis or any of the things that compromise gut health and oral tolerance in general. Lab testing and consultations can be done through Dr. Lawenda’s office or remotely through his IOE website.

https://youtu.be/og-PhNkGbEI

What are the Effects of Dysbiosis on the Intestinal Wall?

The intestinal lining cells have “tight junctions” between them that prevent the gut microbes, food proteins and toxins from entering into the bloodstream and causing systemic immune and inflammatory effects across the body. Intestinal wall leakiness (also known as “leaky gut”) can develop when there is a loss of gut barrier integrity, enabling access into the mucosal wall (causing chronic intestinal inflammation) and, eventually, the bloodstream. Having a healthy microbiome protects the gut wall from developing chronic inflammation and leakiness. The majority of individuals who have dysbiosis (and even intestinal inflammation or a leaky gut) have no obvious symptoms to alert them of this condition, so this can go unnoticed and wreak havoc both in the intestinal tissues and systemically.

Lab Testing for Dysbiosis:

Sending a stool sample to a lab is the best way to know what’s going on inside. Dr. Lawenda often recommends a DNA stool test to many of his patients to assess their overall gut health (one of his favorites is the GI MAP assay). This test was designed to assess a patient’s microbiome from a single stool sample, with particular attention to microbes that may be disturbing normal microbial balance and may contribute to intestinal inflammation and leaky gut. The panel provides a comprehensive analysis of bacteria, fungi, parasites and viruses as well as immune and digestive markers. While a growing number of testing companies offer microbiome tests that are accompanied by dietary recommendations, take these with a pinch of salt; the science is very new and these recommendations are simply based on an automated algorithm, not on you as a biochemically unique individual. (Below, I discuss a combined stool test and probiotic supplement that I recommend).

Should You Take Probiotics and What Are The Risks?

The same microbes that are found in our gut are also in fermented foods, such as yogurt, kefir, kimchi, sauerkraut, miso and cheeses. While eating these foods has been shown to improve the health of the gut microbiome (unless you have intestinal sensitivities or allergies to these foods), studies have been inconclusive about whether probiotic supplements actually improve health outcomes for everyone. You can eat them or drink them, but they won’t necessarily stay and colonize, and they won’t necessarily do you any good. Many questions remain unanswered:

• How is a specific microbiome established in an individual?
• How does our microbiome change over time?
• How does the human body and microbe community interact?
• How does a particular combination of microbes affect nutrition?
• How do changes in diet affect the microbiome?
• How does the microbiome affect immunity and contribute to disease?
• How do antibiotics affect the microbiome?
• How do the microbes in our bodies affect how we respond to various drugs?
• How can a microbiome be altered to improve health?
• Which microbes are helpful and which are not?
• How much or how often someone should consume a probiotic?

One thing we do know is that when your gut microbiome is compromised, studies have found that chemotherapy and immunotherapy may not work as well (REF). Additionally, as noted above, there are numerous health conditions and symptoms that are associated with dysbiosis. These findings have encouraged millions of individuals to start taking supplemental probiotics with the hope that they will improve their health and quality of life. While there are certainly studies reporting treatment and prevention effectiveness of supplemental probiotics, it’s very important to note that there are also some data that have shown that these supplements may have harmful effects:

• Individuals given probiotics after a course of antibiotics have a slower recovery of their normal gut microbiome than those given a placebo (REF)
• Probiotic use can result in a significant accumulation of bacteria in the small intestine that can result in disorienting brain fogginess, rapid and significant belly bloating and discomfort (REF)
• Probiotics given to children in an intensive care unit developed lactobacillus bacteremia (REF)
• In a few cases, mainly involving individuals who were severely ill or immunocompromised, the use of probiotics has been linked to bacteremia or fungemia (REF)
• Fecal transplantation of probiotic organisms (a medical approach for delivering probiotics directly into the intestines) led to an infection and subsequent death of a patient (REF)
• Patients with metastatic melanoma who were taking probiotics while they were on a common immunotherapy drug were 70% less likely to respond to the immunotherapy (REF)
• A preclinical study found that certain mice who were given a probiotic, developed changes in the characteristics of the bacteria which caused intestinal wall damage (REF)

These studies raise questions on the generalizability of the safety of supplementing with probiotics. While there are no hard and fast rules on contraindications for taking probiotics, these are some of the more common recommendations for who should be more cautious with their use:

• Patients with a central venous catheter
• Patients who are critically ill
• Newborns with very low birth weight, clinical instability or catheters
• Patients with severely suppressed immune systems, including people with low white blood cell counts (neutropenia) as a result of cancer treatment
• Individuals with sensitivities or allergies to specific probiotics
• Individuals who are taking certain medications for which there are drug-probiotic interactions

Our recommendation is to check with your cancer care team before taking a probiotic supplement and ask them whether you can safely eat foods containing live bacteria. If they advise against this, do what you can to consume prebiotics (vegetables, fruits, whole grains, beans, etc.) to support the health of the microbes that live in your gut.

Dr. Lawenda’s Favorite Probiotic:

It is important to recognize is that there is no one-size-fits-all probiotic supplement or food. If you are like me and are convinced that taking a probiotic improves gut and systemic health in those with dysbiosis, I first recommend that you get a stool microbiome test to assess for dysbiosis. If my patients have dysbiosis, I suggest they consider taking measures to specifically address their mix of organisms:

• Those with high or low levels of microbes should increase their intake of prebiotics and address the points noted in the section (How does Dysbiosis Develop), above.
• Those who are symptomatic and have high levels of pathogenic microbes might need to be treated with antimicrobial pharmacologic therapies.
• Those with low levels of microbes can be addressed with targeted supplementation.

Targeted probiotic supplementation should be based on lab testing, as there is no other way to know which organisms are deficient. An important added complexity is that over time (days-to-years) one’s microbiome is constantly changing, therefore we need to continue to test for these changes and make adjustments to the probiotic supplementation. There is one company that is the leader in this approach: Sun Genomics. They have developed a commercial probiotic (FLORÉ Precision Probiotics) based on their own stool DNA test. Customers submit a stool sample to the Sun Genomics lab, and they ship back a customized 3-month supply of probiotics to help address their dysbiosis. Every few months, stool testing is repeated and modifications to the probiotic supplements are made. In my opinion, this is the best supplemental approach currently available to help address gut dysbiosis.

Polyphenols Feed Your Microbiome:

The plants you consume are not only great for their prebiotic benefits, but they also contain important compounds called “polyphenols.” Dietary polyphenols are present in fruits, vegetables, cereals, tea, coffee, and wine, among others. Studies have shown their antioxidant, anti-inflammatory, anti-diabetic, anti-cancer, neuroprotective, and anti-adipogenic properties. Because of poor absorption, polyphenols are retained in the intestine for longer time where they enhance the growth, balance and diversity of your gut microbiome.