The modern era of microbiome science

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Prebiotics, probiotics and postbiotics are at the center of human microbiome health, as well as ongoing research and product development.

The human microbiome refers to the organisms (bacteria, fungi and viruses) that reside in and on a person’s body. For the purposes of this article, the use of the term microbiome will be limited to those bacteria.

The Human Genome Project, which cost an estimated US$3 billion, was a 13-year (1990-2003) project that resulted in the first successful sequencing of the human genome. Scientists had hoped that sequencing the human genome would lead to cures for many of today’s chronic degenerative diseases. That goal failed, and sequencing the human genome never led to successful treatments for any diseases.

However, one great benefit that emerged from the project was the development of incredible technology which allows scientists to sequence genomes at a fast, affordable pace. For example, in January 2017, Illumina, a global producer of next-generation sequencing technology, announced its new NovaSeq could sequence a genome in one day for only $100.

The incredible power and speed of the new gene sequencing technology were partly responsible for the government’s funding of the Human Microbiome Project (2007-2012). That endeavor resulted in the publication of over 350 studies, which are viewed as the “birth” of the modern era of microbiome science.

“There was a tremendous amount of knowledge gained from the Microbiome Project and subsequent research on the human microbiome,” explained Nena Dockery, scientific and regulatory manager at Stratum Nutrition. “Families of microbes (mostly bacteria) were identified, and their relative numbers began to be associated with various health benefits and disease susceptibility. Some of the bacterial species that were shown to be particularly beneficial were isolated from human or food sources and commercially grown as a supplemental source of these beneficial species—and the probiotics industry took off. Along the way, it was discovered how important specific strains of bacteria were, which narrowed commercialization down to bacterial strains that could be patented for their benefits.”

She continued, “Prebiotics then began to become recognized as food sources both for the supplemented probiotics and to encourage growth of the body’s own beneficial species. If combined in a product with specific bacteria shown to thrive with certain prebiotics, the term ‘synbiotic’ was used.”

Dockery took particular interest in the developing science. “As part of the research on the body’s native bacteria, it was found that certain bacteria produce byproducts of their metabolism that have substantial benefits to their human host,” she stated. “For example, some produce digestive enzymes, like lactase. Lactase breaks down milk sugar (lactose) and its absence in the body leads to lactose intolerance. Other bacteria—especially those in the colon—produce short-chain fatty acids [SCFAs], such as butyrate, that are very protective against the development of colon cancer. Of course, this type of research was a big ‘Ah ha’ moment for scientists because the microbes (again, mostly bacteria) could produce these byproducts in the broth used to ferment them for commercial production into probiotics; and that resulted in a further study that led to the introduction of postbiotics.”

Probiotics

Most probiotics currently on the market are designed to work in the gut. The intestinal tract, particularly the lower intestine, is the home to trillions of microorganisms that provide a variety of benefits, mostly related to digestion and immune functioning. However, medications, especially antibiotics, along with certain disease conditions, diet, genetics and lifestyle choices, all play a role in the composition of an individual’s microbiome. Probiotics are designed to support healthy functioning of the body’s own microbiome and fill in the gaps where deficiencies have developed.

It is now known that the immune benefits of the body’s protective microbiome don’t begin in the gut, but in the oral cavity, where pathogenic microbes most often enter the body.1 The oral cavity is home to as many different species of bacteria as the gut; and these bacteria can form an extremely strong barrier against invaders, influencing the health, not only of the teeth and gums, but extending into the throat and ear canals, and indirectly, throughout the entire body.

Dockery suggested, “To a certain extent, these good bacteria function through competitive inhibition, but more importantly, some strains of bacteria like the beneficial oral cavity species, Streptococcus salivarius, can produce compounds called bacteriocin-like-inhibitory-substances (BLIS). These compounds are highly inhibitory to specific pathogenic bacteria. Probiotics derived from indigenous strains of these beneficial bacteria may help provide a front-line protection against unfavorable strains entering the body through the mouth and nose. Some of these strains, such as S. salivarius K12 have been extensively researched for safety and their ability to colonize in the human oral cavity.”2-8

Another indigenous strain of S. salivarius is M18, which has several unique characteristics that make it a beneficial component of the oral microbiome. S. salivarius M18 produces BLIS compounds that inhibit several species of common bacterial species that contribute to tooth decay and gingivitis. It also secretes two enzymes that make the oral cavity less favorable to deleterious species. Urease is an enzyme produced by M18 that helps raise the pH of the oral cavity environment, making it less conducive to acidogenic bacterial strains that weaken tooth enamel. M18 also produces a dextranase that helps break down dextran, a carbohydrate that is an integral component of dental plaque. BLIS M18 is a probiotic sourced from S. salivarius M18 that has been shown in several studies to help promote healthy teeth and gums.9-12

Prebiotics

Present in fiber-rich foods such as fruits, vegetables and whole grains, prebiotics are a type of fiber the human body cannot digest. Dockery noted the benefits of dietary fiber are well-known, impacting such diverse areas as cardiovascular health, digestive health and weight.13 Most dietary fiber sources are complex polysaccharides. However, this has expanded to include oligosaccharides, which are composed of fewer monosaccharides (simple sugars). Oligosaccharides now make up most commercially marketed prebiotic fiber.

Prebiotics persist intact through the digestive tract to the colon where they are fermented by bacteria and other microorganisms. Consumption of prebiotic foods or supplements can help ensure an optimal food source for colonic bacteria and production of the beneficial compounds (such as the SCFAs) resulting from the fermentation process.

Though prebiotics can fairly easily be obtained through the ingestion of certain foods (such as oats that contain beta-glucan, and apples, which contain pectin), many of the best sources for prebiotic fiber are foods such as konjac root and seaweed, which are not regular parts of the Western diet. As such, prebiotic supplements are gaining in popularity.

Postbiotics

“Currently, there is no consistency in what is sold as a postbiotic,” Dockery maintained. “Some companies market products identified as postbiotics that are a blend of the beneficial byproducts of microbial metabolism found in the supernatant or even single byproducts such as butyrate. However, the International Scientific Association of Probiotics and Prebiotics (ISAPP) recently set the definition as 'A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.' This definition includes the presence of killed microbial cells and cell fragments (usually from heat treatment) but notably omits the requirement of the supernatant, though it could be included in a postbiotic product.”

She acknowledged postbiotics appear to be the latest trend in the “-biotics” industry and do have some distinct manufacturing and marketing advantages over probiotics. Most notably: since they are not live microbes, shelf stability and survival through the gut can be much more predictable.

Alexis Collins, product manager at Stratum Nutrition, said, “It is a relief to have an esteemed scientific body such as ISAPP provide us with a comprehensive definition of postbiotics. This will not only provide much-needed clarity for our customers, but will also be the kickoff for postbiotic education for the end consumer.”

Stratum offers LBiome, a human strain-derived, heat-treated postbiotic (Lactobacillus LB), the latter of which has been researched in postbiotic form for over a century, with 12 published clinical studies showing digestive health support for both adult and pediatric populations.14-21 Collins noted LBiome provides the digestive benefits of a probiotic and the formulation flexibility of a spore, with none of the stability or manufacturing concerns.

LBiome cells adhere to the gut lining, forming an enhanced environment for the gut microbiome, all while simultaneously strengthening the gut lining by supporting a healthy brush border and tight junctions.22 In addition, recent published research has shown the ingredient to be bifidogenic, increasing populations of several species of beneficial Bifidobacterium in both an in vitro cell culture and in an ex vivo human fecal fermentation system.

Growth of the biotic industry

According to the MarketsandMarkets report, "Human Microbiome Market by Product (Prebiotics, Probiotics, Food, Diagnostic Tests, Drugs), Application (Therapeutic, Diagnostic), Disease (Infectious, Metabolic/Endocrine), Research Technology (Genomics, Proteomics, Metabolomics) - Global Forecast to 2028," the global human microbiome market is projected to reach US$1.6 million by 2028. This is up from $894 million in 2025, at a compound annual growth rate (CAGR) of 21.3% through the time period.

Dockery concluded, “Few other segments within the dietary supplement and functional foods industries have expanded and diversified to the extent that the ‘-biotics’ segment has. This has presented tremendous opportunities for continued growth, and at the same time has resulted in the expected challenges such as where and when NDINs [new dietary ingredient notifications] might be required, to the splitting of the Lactobacillus genus. At the same time, this expansion provides exciting opportunities for the introduction of new ingredients that will safely and effectively provide tremendous benefits that can potentially be customized to meet specific needs in the end consumer.”

The research on prebiotics, probiotics and postbiotics continues to expand as more information is uncovered about the positive role the human microbiome plays in supporting and maintaining human health.

Jacqueline Rizo is a content writer who specializes in B2B articles and white papers for the natural products industry on behalf of Stratum Nutrition.

References

1 Burton JP et al. “Beneficial microbes for the oral cavity: time to harness the oral streptococci?” Benef Microbes. 2011;2(2):93-101.

2 Di Pierro F et al. “Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media.” Int J Gen Med. 2012;5:991-997.

3 Di Pierro F et al. “Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults.” Expert Opin Biol Ther. 2013;13(3):339-343.

4 Di Pierro F et al. “Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children.” Drug Healthc Patient Saf. 2014;6:15-20.

5 Di Pierro F et al. “Oral use of Streptococcus salivarius K12 in children with secretory otitis media: preliminary results of a pilot, uncontrolled study.” Int J Gen Med. 2015;8:303-308.

6 Di Pierro F et al. “Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children.” Eur Rev Med Pharmacol Sci. 2016;20(21):4601-4606.

7 Di Pierro F et al. “Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo-tonsillitis and acute otitis media in children: a retrospective analysis in not-recurrent pediatric subjects.” Pediatrica. 2018;70(3):240-245.

8 Marini G et al. “Pilot study to explore the prophylactic efficacy of oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngo-tonsillar episodes in pediatric patients.” Int J Gen Med. 2019;12:213-217.

9 Di Pierro F et al. “Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.” Clin Cosmet Investig Dent. 2015;7:107-113.

10 Bardellini E et al. “Does Streptococcus Salivarius Strain M18 Assumption Make Black Stains Disappear in Children?” Oral Health Prev Dent. 2020;18(1):161-164.

11 Scariya L et al. “Probiotics in Periodontal Therapy.” Int J Pharma Bio Sci. 2015;6(1):242-250.

12 Burton JP et al. “Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial.” J Med Microbiol. 2013;62(Pt 6):875-884.

13 Slavin J. “Fiber and prebiotics: mechanisms and health benefits.” Nutrients. 2013;5(4):1417-1435.

14 Boehm G et al. “Prebiotics and immune responses.” J Pediatr Gastroenterol Nutr. 2004;39:pS376.

15 Simakachorn N et al. “Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children.” J Pediatr Gastroenterol Nutr. 2000;30:68-72.

16 Salazar-Lindo E et al. “Effectiveness and safety of Lactobacillus LB in the treatment of mild acute diarrhea in children.” J Pediatr Gastroenterol Nutr. 2007;44(5):571-576.

17 Lievin-Le Moal V et al. “An experimental study and a randomized, double-blind, placebo-controlled clinical trial to evaluate the antisecretory activity of Lactobacillus acidophilus strain LB against nonrotavirus diarrhea.” Pediatrics. 2007;120(4):795-803.

18 Bodilis JY. “Controlled clinical trial of Lacteol Fort compared with a placebo and reference drug in the treatment of acute diarrhea in the adult.” Medecine Actuelle. 1983;10:232-235.

19 Xiao SD et al. “Multicenter, randomized, controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrhea.” Adv Therapy. 2003;20:253-260.

20 Kor JY et al. “Lacteol Fort Treatment Reduces Antibiotic Associated Diarrhea.” Singapore Fam Physician. 2010;36(4):46-49.

21 Canducci F et al. “A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates.” Aliment Pharmacol Ther. 2000;14(12):1625-1629.

22 Warda A et al. “A postbiotic consisting of heat-treated Lactobacilli has a bifidogenic effect in pure culture and in human fermented fecal communities.” App Environ Microbiol. 2021;87(8):e02459-20.

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