This is an exciting time in the study of the human gastrointestinal tract. The enthusiasm is largely due to recent scientific developments and rapidly accumulating molecular biology data on several fronts. Perhaps most significant are large-scale efforts to define the constituents of a healthy human microbiome and its functional capacity.
These efforts are followed by characterizations of the microbiome in particular pathologic states with microbial imbalance—dysbiosis—explored either as cause or effect. It is anticipated that these studies of the connections between certain disease and dysfunction states and what is familiarly termed a “healthy gut” will continue to provide further insight into the host-microbiome interactions that contribute to contribute to maintaining health and disease risk reduction.
It’s been said that the digestive system is the most important organ of the immune system. Moreover, the paradigm recently identified as “gut-brain interaction” points to the g.i. tract as a center for whole-body health.
Consumers are now regularly exposed to the idea of a dietary approach targeting the microbiome. Increasingly, they are becoming aware that the maintenance of digestive health can be the path to an improved state of health and well-being.
In turn, as more such information comes to light, application of not only the knowledge but the ingredients—both the living microbes and the ingredients that support them and their environment—will translate to increased application in better-for-you foods and beverages.
The microbial populations that reside in and on the human body constitute our microbiota. The genes they encode are known as our microbiome. (The term “microbiome,” however, has now come to be used interchangeably with “microbiota” to designate the colonies of microorganisms residing within the body.)
This complex community contains taxonomic groups from across bacteria, eukaryotes, viruses, and at least one known archaeon (a type of single-cell organism that resembles a bacterium), that interact with one another and with the host, impacting human health and physiology.
More importantly, diet has a direct effect on this community. It might be possible to shift and enhance the microbiome by adding friendly bacteria from foods. Examples of foods with friendly bacteria include yogurt, cheese, kefir and other fermented dairy or through other foods probiotic food sources, such as sauerkraut and kimchi (fermented cabbage) and natto (soy beans fermented with Bacillus subtilis natto).
Other foods and some ingredients could help create an environment that can encourage the flourishing of these friendly microbes. Certain starches and fibers are “prebiotic”; that is, they promote the growth of desirable microbes, usually by acting as a ready energy source.
The microbiota is involved in energy harvest and storage, as well as in a variety of metabolic functions such as fermenting and absorbing nutritionally unavailable carbohydrates. This latter trait has probably acted as a template toward the establishment of bacteria as human symbionts.
Perhaps even more importantly, the gut microbiota interacts with the immune system, providing signals to promote the maturation of immune cells and the normal development of immune functions. It is this powerful connection to immunity that led to the recent shift in the development of foods, beverages, and supplements for digestive health from simple regularity to the aforementioned standard of complete physiological health.
This “upgrade” in consumer awareness and impetus toward eating for better digestive health to possibly improve innate immunity also has grown to include weight management.
Evidence supporting the link between a host’s microbiota, digestion, and metabolism has been mounting. In an analysis of humans and 59 additional mammalian species, the evidence indicates that microbiome community structures differ as a function of diets among other influencing factors.
Since the most effective health measures and novel innovations will likely need to address multiple gut health domains simultaneously, nutritional (as opposed to pharmacologic) interventions are particularly appealing and well poised for this purpose. The challenge will be to define how and when to orchestrate nutritional manipulation of the microbiome for a given individual facing a given set of constraints and pathologies.
Whole Body Health
Gut health has grown to become a buzzword in contemporary culture. Increasing numbers of studies suggest potential sensational links between the gut and such diverse areas as our mood, weight, and cognition. The current debates on the digestive system and our physical and mental health, however, are not without long-standing precedent.
The stomach occupied a central place in the development of medicine in the 19th century. The number of medical, literary, and popular publications on digestion proliferated from this period onwards. With the exception of under- and over-nutrition, however, few scholars examined the cultural and sociological significance of the gut in the modern period, confirming the lowly and frankly mysterious status the abdomen has had in the Western intellectual tradition.
The clinical preoccupation with the digestive system from the Renaissance through the Industrial Revolution developed a new urgency in the 19th century as a result of the rapid progress of general internal medicine, general surgery, and geriatrics. Moreover, there was increased concern with the stomach as a site of one’s personal and public identity. The obsession with the gut during this period was a highly cosmopolitan phenomenon crossing many fields and fashions.
It was during this period that the notion of “food as medicine” seemingly made its way back into health practices. (Think: John Harvey Kellogg and Sylvester Graham and their respective invention and promotion of corn flakes, graham flour, and “roughage,” as well as vegetarianism, soy milk, and other soy foods.)
While fiber and whole grains experienced a resurgence that began then, they have periodically enjoyed renewed popularity over the years—most recently in the 1980s when associated with heart health. However, their component functional starches and fibers currently are trending quite high as a result of the digestive health boom, because they are associated with prebiotic benefits—that is, feeding the microbiota.
The most common form of digestive dysfunction, Irritable Bowel Syndrome (IBS), is believed to affect one in five Americans. Its landscape of symptoms involves one or more of the following four domains: the microbiome, the epithelium (barrier function and absorption), the immune system (innate and adaptive), and metabolism. There is much evidence to suggest that an “unbalanced” microbiome influences the other areas as well.
Since a role for the microbiota in IBS is suspected, therapies that alter the microbiota, including dietary changes, probiotics, and antibiotics, have shown encouraging successes. However, it should also be noted that results of such therapies have been inconsistent.
One pair of Australian studies investigated dietary intervention for IBS using the now-popular “low-FODMAP” diet. FODMAP stands for “Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.” The diet calls for restricted intake of certain fermentable substrates compared to a typical diet.
In a small number of Australian patients with IBS, the low FODMAP diet improved symptoms and resulted in changes in gut microbiota. Interestingly, the results also included reductions in putatively healthful bacteria, such as those in butyrate-
producing Clostridium cluster XIVa.
A proposed pathway involved in IBS is through a microbiota-gut-brain axis, linking changes in the gut to symptom perception in the central nervous system.
A recent, thought-provoking study demonstrated that the intake of a probiotic-rich fermented milk product resulted in alterations in brain activity in response to visual-emotional stimuli, as measured by functional magnetic resonance imaging. This was compared to the intake of a control product.
The study of IBS is challenging due to the lack of specific diagnostic tests and the possibility of heterogeneous and variably penetrant etiologies. There could be a large subset of persons for whom microbiota changes are particularly important and for whom therapies to affect microbiota composition and function might be beneficial.
For product developers targeting the recent upsurge in low-FODMAP diet adherents, avoiding the targeted ingredients can make for limited options. All types of beans and peas, garlic and all types of onions (including shallots and leeks), most grains, most fruits, and processed foods are either limited or off limits.
Evidence for a linkage of microbiome and immunologic function is already strong, and growing. Digestive health and the microbiota begins at birth. The natural infant gut microbiome also appears to be in some ways shaped by the numerous innate oligosaccharides in breast milk. The microbiome of a breast milk fed infant is dominated by a single Bifidobacteria species–B. infantis–that originates in the mother’s gut microbiome.
This keystone commensal organism appears to have been generationally lost in the developed world and possibly through alternative birthing processes and the use of infant formula. But the natural infant gut microbiome is resilient and can be re-established shortly after birth. This has launched such preëmptive interventions as a “gut microbiome remodeling product” that could herald a new era in digestive health promotion.
The human body, in this case, is highly selective. Human milk oligosaccharides are not an all-purpose food for all Bifidobacteria. In 2006, Bruce German, PhD, et alia at UC Davis discovered that these unique sugars selectively nourish one subspecies: Bifidobacterium longum infantis. As long as the human milk oligosaccharides are provided, this subspecies will outcompete any other gut bacterium, including potential pathogens.
A related subspecies, B. longum longum grows weakly on the same sugars, and Lactobacillus rhamnosus GG, a common fixture of probiotic-enriched yogurts, doesn’t grow at all. Another probiotic mainstay, B. bifidum, does slightly better, but is a “fussy eater”—it breaks down a few human milk oligosaccharides and takes only the components it likes.
By contrast, B. infantis devours every last bit of these favored carbohydrates using a cluster of 30 genes—a comprehensive cutlery set for eating. No other Bifidobacterium has this
genetic cluster; it is unique to B. infantis. Human milk contains unique substances to nourish this microbe, and it, in turn, might have changed over time to dine on this ingredient with relish.
Many gut-friendly bacteria release short-chain fatty acids (SCFAs) when they eat certain sugars, fibers, and starches, and B. infantis is no exception. The SCFAs it releases feed the infant’s gut cells and encourages these cells to make adhesive proteins. Those proteins seal the gaps between the cells, keeping microbes out of the bloodstream. The process also stimulates anti-inflammatory molecules that calibrate or prepare the immune system.
These changes only happen when B. infantis feeds on human milk oligosaccharides. If, instead, it gets lactose (the dominant sugar in breast milk), it survives but doesn’t engage in any “give and take” with the baby’s cells. In other words, the microbe’s full beneficial potential is unlocked only when it feeds on breast milk.
Microbes liberate SCFAs from nutritionally unavailable dietary fibers, such as resistant starch, some forms of inulin, and other types of oligosaccharides.
These SCFAs are an important energy source for intestinal mucosa cells and critical for modulating immune responses and important for modulating tumorigenesis in the gut. One particularly abundant and bioactive SCFA is butyrate.
Butyrate plays a complex role in colon cancer that seems to be both concentration and context dependent. This was illustrated by two recent animal studies. Butyrate was reported to actually promote tumorigenesis in a study on genetically altered mice.
Conversely, butyrate was reported to inhibit tumorigenesis in mice deficient in a receptor for butyrate. Further investigations into the role of butyrate produced by microbiota in colitis and colorectal cancer are needed.
In humans, however, there has been encouraging evidence that these fermentable carbohydrates reduce colon cancer risk and provide other health benefits, such as weight management and blood sugar balance. Incorporating prebiotic ingredients into foods and beverages can be promoted as beneficial based on a number of studies; in fact, a health claim was recently permitted for resistant starch from high-amylose maize in relation to blood-sugar management.
Even more provocative research has revealed a key role for Bacteroidales in the immuno-stimulatory process. It might be possible to beef up a patient’s antitumor response with some probiotic strains.
Analysis also has suggested that certain bacteria in the Bacteroides and Burkholderia genera are responsible for the antitumor effect of the microbiome. To confirm that possibility, researchers have transferred the microbes into mice with no intestinal bacteria. The influx of microbes was shown to have amplified the animals’ response to one checkpoint inhibitor (a type of drug or compound that blocks certain proteins to keep them from functioning).
Future pathways for research into digestive health will explore how genes influence the composition of the gut microbiota, how microbial genes influence the expression of human genes, and how diet may influence the gut microbiota and possibly the expression of some human genes in conditions such as obesity.
As new information is revealed, product developers could be able to create whole new categories of products that cater to the proper care and feeding of our digestive system, perhaps even through the emerging area of personalized nutrition.
Originally appeared in the September, 2017 issue of Prepared Foods as Good Digestion.
It’s the Raisins
by Jim Painter, PhD, RDN
Raisins contain nutritional properties that are beneficial for digestive health, including dietary fiber. While raisins “officially” provide 10% of the FDA’s daily recommended fiber, US labeling guidelines for dietary fiber do not include inulin and soluble fibers. Because of this, raisins are listed as containing 1.6g of dietary fiber per 43g serving (6% of the Daily Value). Raisins contain inulin, a fructoligosaccharide classified as a soluble fiber. It bypasses digestion and is fermented in the lower g.i. tract, feeding colonic bacteria.
Research has shown this is beneficial for increasing helpful gut microbiota and decreasing pathogenic gut microbiota species, in addition to decreasing triglyceride and cholesterol levels. A 100g serving of raisins contains 5g of fructooligosaccharides. These fibers are not found in the original grapes; they is produced through the processing of grapes into raisins. The human gut is believed to comprise 80% of the body’s immune system and microbiota form an interface between contents fed into the gut and how the body responds in the form of inflammation, cardiovascular disease, digestive health, and allergies.
But raisins are more than sources of fiber when it comes to digestive health. They also contain tartaric acid, which has been shown to decrease intestinal transit time from an average of 54 +/-6 hours without raisins to 42 +/-6 hours with the consumption of 168g of raisins daily for two weeks.
Another compound in raisins, polyphenolic phytochemicals called
proanthocyanidins, turn out also to have a digestive effect. They are associated with resistant fibers in digestion, and they similarly ferment in the lower g.i. tract. Research has demonstrated that they also release metabolites that have potential health benefits.
Jim Painter, PhD, RDN, is an adjunct professor at the University of Texas, Houston, School of Public Health. He can be reached at jimpainterphd@
gmail.com or www.drjimpainter.com.
Emerging science is suggesting that our connection to the circadian light-dark cycles plays an important role in governing the microbiome, according to John Douillard, DC, author of Eat Wheat. While probiotics might have an inevitable future in medicine, the all-too-common lifestyle most Westerners lead is one completely out of sync with the natural rhythms of nature. Whether stress, sleep deprivation, or the replacement of darkness with artificial light, the result is an alteration of the hormone melatonin and cortisol rhythm, notes Douillard, both of which impact the microbiome. Melatonin is commonly called the “sleep hormone” because it regulates the sleep cycle. “When the sun sets at 6 PM and we regularly turn the lights off at 11PM, there is a delay in melatonin production,” Douillard explains. “Optimal melatonin production at night not only regulates sleep but also acts as the body’s most powerful antioxidant detox agent and a regulatory agent of a healthy microbiome.” For processors, tart cherries are relatively high in melatonin compared to other melatonin-rich food ingredients such as goji berries, tomatoes, pomegranates, and asparagus. And nuts, cheeses, legumes, and meats (such as turkey) are good sources of tryptophan, a precursor of melatonin.
A recent short-term, well-controlled study to “characterize the interaction between the infection and host responses under controlled conditions in human volunteers with use of probiotics” demonstrated that one specific probiotic strain, Bifidobacterium lactis Bl-04, could “modify the innate immune system response following supplementation and the inflammatory response in the nose following rhinovirus infection.” Meanwhile, a longer (five months) human clinical trial showed that the B. lactis Bl-04 probiotic also was able to reduce the risk of upper respiratory illness episodes. When it comes to respiratory system immunity, it could be that certain probiotics can help all of us breathe a little easier.
Last summer, results were published from a randomized, double-blind, placebo-controlled intervention study regarding the safety and tolerance of three probiotic strains in healthy infants. The multi-center study was conducted by a team from Madrid University, Spain, and individually tested the Lactobacillus helveticus Rosell-52, Bifidobacterium infantis Rosell-33, and B. bifidum Rosell-71 strains of probiotic bacteria. The microbes all were previously shown to help prevent the reoccurrence of winter infections in children. This 2-month intervention study involved 221 healthy infants aged 3-12 months, divided into four groups: placebo, and each of the three probiotic strains. The results led the researchers to conclude that, “the use of the three probiotic strains in infancy is safe, and well tolerated,” with “no serious adverse events.”