Feeding Friendly Flora: Prebiotics Have Key Role in Immune Resilience

The gut microbiome and the human immune system have a complex synergistic relationship that we are just beginning to understand.

Research on this subject has exploded over the last decade, and the findings are redefining fundamental notions of what it means to be healthy, and, really what it means to be “human.” The immune system–and by extension human health–is highly dependent on the health and diversity of the microbial world inside the intestines.

From a clinical perspective, much of the emphasis has been on probiotic supplementation for restoring and supporting “friendly” organisms, especially in the wake of antibiotics, other disruptive pharmaceuticals, poor diet, or exposure to environmental toxins.

But it is becoming clear that probiotics alone have their limits, and that maintaining a healthy GI ecosystem requires more than simply swallowing a few lactobacillus capsules.

That’s where prebiotics come in.

Researchers around the world have identified a number of different plant fibers, phytonutrients, and metabolites that promote the growth of friendly flora. When combined judiciously, they become a key factor in the microbiome restoration equation.  

In short, we need to feed our friends, if we want them to feed us.

Probiotics alone have their limits, and that maintaining a healthy GI ecosystem requires more than simply swallowing a few lactobacillus capsules. That’s where prebiotics come in.

“There are multiple layers of interaction between microbes, the gut, and the immune system,” says Weston Bussler, PhD, a nutrition scientist working at the Standard Process Nutrition Innovation Center (NIC), Kannapolis, NC.

“Gut microbes regulate our immune cells and their production of pro-inflammatory and anti-inflammatory signals. They help the GI tract respond to non-native, potentially pathogenic or opportunistic organisms. They also produce a lot of bioactive metabolites and short chain fatty acids themselves, and they interact with phytochemicals in our food,” he explained in an interview.

For example, cruciferous vegetables contain many glucosinolate compounds that are in non-bioactive forms. Certain gut microbes produce enzymes that can hydrolyze glucosinolates into biologically important sulfur-containing compounds like sulforaphane.

While Bifidobacteria and Lactobacillus are the two most prominent and widely researched groups of gut bacteria, there are many other bugs that also play important roles, Dr. Bussler told Holistic Primary Care

2’-FL resists digestion in the upper GI tract, meaning that it enters the intestines intact. Once there, it and the other milk oligosaccharides serve a dual function: they act as decoy binding sites for potential pathogens, and as prebiotics to nourish beneficial organisms.

A main focus of Dr. Bussler’s work over the last year has been the development of a comprehensive prebiotic formula that brings together several different ingredients to nurture the growth of beneficial bacteria. Called GI Stability, the new product which launched last year, is useful for everyday microbiome maintenance, as well as for more acute situations such as symptomatic dysbiosis, or post-antibiotic microbiome restoration.

GI Stability contains the following:

2-Fucosyllactose (2’-FL): This is one of a number of compounds called Human Milk Oligosaccharides (HMOs), found naturally in human breast milk. HMOs are complex glycans that play an important role in establishing a healthy microbiome in breast-fed infants. 2’-FL and the other HMOs are linked to immune system development in infancy and early life.

Chemical structure of 2-Fucosyllactose (2′-FL)

After lactose, HMOs are the most common form of sugar in breast milk. Over 1,000 different ones have been identified. Generally, 2’-FL is the most prevalent of the HMOs.

2’-FL resists digestion in the upper GI tract, meaning that it enters the intestines intact. Once there, it and the other milk oligosaccharides serve a dual function: they act as decoy binding sites for potential pathogens, and as prebiotics to nourish beneficial organisms.

Compared with the placebo, HMO supplementation for two weeks increased the abundance of Actinobacteria and Bifidobacteria, both of which are beneficial to humans.

“The terminal monosaccharide on 2’-FL is a fucose sugar. The bond it has to the other molecular components is unique, and it is hard for most organisms to break it down,” explained Dr. Bussler. Fortunately for us, the organisms that can digest and assimilate 2’-FL are beneficial for our own digestion and metabolism.

Bolstering Bifido

Several species of Bifidobacteria grow very well on 2’-FL, so well in fact that it was originally named “Bifidus factor.”

In a landmark 2010 report, researchers at University of California, Irvine showed that friendly flora like Bifidobacterium longum subsp. infantis, Bacteroides fragilis, and Bacteroides vulgatus efficiently metabolize HMOs, whereas problematic bugs Enterococcus, Streptococcus, Veillonella, Eubacterium, Clostridium, and Escherichia coli are unable or, at best, only partially able to grow in HMO-rich media (Marcobal A, et al. J Agric Food Chem. 2010).

HMOs also prevent pathogen attachment to mucosal surfaces, reduce mucosal leukocyte infiltration and activation, and modulate immune cell responses (Bode L. Glycobiology. 2012).

The benefits of HMOs are not limited to infancy.

Several years ago, Danish researchers studied the effects of 2’-FL supplementation in 100 healthy adults, randomized to 2’-FL, lacto-N-neotetraose, a combination of those two supplements, or a placebo. This was the first RCT looking at the possibility of modulating the adult microbiome with HMOs.

They found that compared with the placebo, HMO supplementation for two weeks increased the abundance of Actinobacteria and Bifidobacteria, both of which are beneficial to humans.

Based on their observations, the authors concluded that, “supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria.”  At doses up to 20 g 2’-FL was well tolerated.

The 2’-FL that Standard Process uses in its new GI Stability formula is not derived directly from human milk. Rather, it is a bioequivalent form produced at large scale via an industrial fermentation process.

Dr. Bussler said that there are several studies ongoing that explore the impact of at 2’-FL supplementation in adults, though several have been interrupted by the COVID-19 pandemic.

Collinsonia Root (Collinsonia canadensis). Known colloquially as Richweed or Stone Root, Collinsonia is a perennial herb in the mint family, indigenous to eastern North America.

Collinsonia canadensis (Image by Josephine Billeter)

It has a long history of use among Native Americans on the Eastern Seaboard, They used the leaves topically to promote wound healing, and also made teas to treat digestive and urinary problems. By the mid-1800s, it was a mainstay in the herbal pharmacopeia of European-American settlers who used it as a diuretic, to promote digestion and elimination, and to reduce hemorrhoids and strictures.

As was the case with a lot of herbs, by the late 1800s, Collinsonia was pushed to the margins and nearly forgotten as the emerging pharmaceutical industry pushed “modern” chemical-based medicines. Today, relatively few people even know about it.

As was the case with a lot of herbal medicines, by the late 1800s, Collinsonia was pushed to the margins and nearly forgotten as the emerging pharmaceutical industry pushed “modern” chemical-based medicines. Today, relatively few people even know about it.

“At Standard Process, we’ve been using Collinsonia in our formulas since the mid 1950s,” Bussler said. Though it is not a direct laxative, it does promote bowel regularity—an important piece of the microbiome puzzle.

Okra and Beet Powder: These two highly nutritious vegetables are rich in both soluble and insoluble fiber, which are vital for healthy elimination and for feeding friendly gut flora. Beetroot powder also provides betalins which promote nitric oxide production and improve blood flow.  The okra and beet powders are incorporated into the GI Stability formula primarily to feed the gut microbes, but they do give the added benefit of a wide range of minerals and phytonutrients for the human host.

Beets and Okra are both rich sources of soluble and insoluble fiber which feed friendly flora and promote regular elimination. Beetsalso promote nitric oxide production and improve blood flow.

GI Stability is unique in that it is the first product on the market to deliver 2’-FL in a chewable wafer form. Two of the wafers contain 1,666 mg of 2’-FL. It can be used as a stand-alone digestive support product, or in combination with probiotics. It is naturally sweet, owing to the 2’-FL, so it contains no added sweeteners.

For short-term treatment of heavily symptomatic dysbiosis, or conditions like traveler’s diarrhea, Bussler recommends taking up to 6 wafers per day. This gives close to 5 grams of 2’-FL, which in some cases is enough to remodel the microbiome by itself, even without addition of probiotics.

For general GI support and long-term microbiome maintenance, two wafers per day is sufficient.

In a pre-launch pilot study, Bussler and his colleagues found that GI Stability was very well-tolerated by the study participants. A few experienced increased flatulence, but this was not a significant problem.

Standard Process is planning a larger clinical trial to characterize the efficacy of this unique formulation for modulating the gut microbiome.

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