Microbiome mysteries: What don’t we know?

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Exploration of the human microbiome has exploded since 2007 when scientists at the National Institutes of Health (NIH) Common Fund launched the Human Microbiome Project (HMP)¹. This groundbreaking study gave way to a deeper understanding of how trillions of microorganisms living in our bodies-including bacteria, viruses, fungi, and even parasites-can influence human health.

“The way we understand the human microbiome has changed phenomenally in a relatively short space of time,” observes Lucien Harthoorn, PhD, research and development director at UK-based prebiotics development company Clasado Biosciences.

Yet, while this vast body of science has uncovered numerous ways the microorganisms within us impact everything from digestive wellbeing to maternal health to immunity and more, many questions remain.

A second phase of the Human Microbiome Project-called the Integrative Human Microbiome Project (or iHMP)-was initiated to determine how the microbial makeup of subjects influenced specific health conditions and disease states.

Anke Sentko, vice president of regulatory affairs and nutrition communication for Beneo (Germany), says iHMP examined “the role of the microbiome in human health and disease through a study of the changes occurring in the microbiome and host over time.” The three model conditions examined by iHMP included pregnancy and preterm birth, inflammatory bowel diseases (IBD), and type 2 diabetes.

Findings from this second phase will help to characterize these conditions and predict the onset of disease or patient outcomes,” she explains. Also, iHMP may help to identify new opportunities for dietary interventions in the future, Sentko suggests.

Ahead, we look at some of the research objectives of current microbiome studies in the works.

The Multi-Omic Microbiome Study Pregnancy Initiative (MOMS-PI)

One study within iHMP analyzed how the microbiome of expectant mothers can correlate to preterm birth.²

Researchers found that pregnant women who delivered preterm (prior to 37 weeks gestation) had significantly lower levels of the bacteria Lactobacillus crispatus and elevated levels of other microorganisms within the Prevotella species and nine other taxa. The study also found that elevated levels of these specific microorganisms were correlated with proinflammatory cytokines in the vaginal fluid. Notably, these elevated taxa are often linked to vitamin D deficiency.

Inflammatory Bowel Disease Multi’omics Database (IBDMDB)

Another clinical trial within the iHMP examined the dysbiosis of the microbiome among those with inflammatory bowel disease such as Crohn’s disease and ulcerative colitis.³ It’s estimated that approximately three million Americans live with some form of IBD, according to the Centers for Disease Control.⁴

The study identified clear microbial features in hosts with IBD. For instance, an unclassified Subdoligranulum species was significantly reduced in IBD subjects, potentially interfering with bile acid metabolism and short-chain fatty acids. Further research is needed to determine if this reduction was host or microbiome driven.

Integrated Personal ’Omics Project (IPOP)

With data from the World Health Organization estimating 422 million people worldwide have type 2 diabetes, scientists are seeking ways to better understand this disease.

This iHMP study analyzed 106 healthy subjects as well as those with prediabetes for four years. Researchers observed many notable differences in the microbiome of those with insulin resistance, prediabetes, and healthy subjects. For example, during immune system challenges such as a respiratory viral infection, healthy participants, participants with insulin resistance, and those with insulin sensitivity all exhibited significantly different molecular and microbial changes.

Fiber and Flora

In addition to the work done through HMP and iHMP, major studies of the microbiome are being conducted around the world. The journal Nature estimated over $1.7 billion has been invested in research of the human microbiome (20% of that going to the HMP and iHMP).⁵

This massive investment in research has, of course, spurred innovation in the dietary supplement and functional food and beverage industries, particularly in the area of probiotics and prebiotics.

“The information generated by…[The Human Microbiome Project] is available for use by researchers and manufacturers alike, which has huge benefits to the industry,” comments Clasado Biosciences’ Harthoorn. “Businesses of all sizes now have access to insight and data on the building blocks of human health, bringing unique viewpoints and ideas to the market accordingly. As the industry progresses, efforts are being made to better understand and interpret the data, and more clearly identify how it might directly lead to the improvement of human health.”

Oliver Hasselwander, development leader, microbiome venture, DuPont Nutrition & Biosciences (Copenhagen, Denmark), points to probiotic supplementation as potential catalysts for a healthy microbiome. “Probiotics can elicit their health benefits through several mechanisms, such as modulation of composition or activity of the microbiome, of the immune system, systemic metabolic responses, via the central nervous system, improving epithelial barrier function, and increasing colonization resistance against pathogens⁶,” he explains. These actions are mediated by key effector molecules; metabolites or enzymes, such as lactase; and bile salt hydrolases.

Meanwhile, the lack of dietary fiber in the typical Western diet has led to a surge in interest in prebiotics. Prebiotics could also have a significant effect on boosting the growth of beneficial bacteria in the gut, notes Harthoorn. “These bifidobacteria are crucial to establishing and re-establishing a healthy balance of the microbiota composition, which we call eubiosis.”

Further Exploration

Stephen O’Hara, CEO of the UK-based life science company Optibiotix, suggests we’re in the “very early stage of a revolution in healthcare where we will start to see pre- and probiotics that may manipulate certain aspects of the microbiome, and so improve healthcare.” He points to science that is seeking ways to “precision engineer the microbiome to increase the presence of a particular bacterial species and metabolites, their gene expression, their enzymes, and even short-chain fatty acids.” Hypothetically, this could also be done to reduce the levels of microbial species linked to disease states. “I think the future lies in the targeted manipulation of the microbiome,” he says.

Of course, continued research is needed to see these interventions in action. “While we understand and can demonstrate that the microbiome can be modulated, there are still gaps in demonstrating that the role of the microbiome is causally linked to positive health benefits, particularly in human clinical studies,” says DuPont’s Hasselwander. He points to continued areas of interest and exploration including how the microbiome impacts nutrient and medication bioavailability and function; research of how digestive health impacts brain function, often called “the gut-brain axis;” and how microbial intervention could impact weight gain and obesity.

What’s abundantly clear is that consumers are paying attention and are looking for ways to improve their health by way of the microbiome. “Health Focus International’s 2018 Global Trend Study found that among those surveyed, 42% were very or extremely interested in the gut microbiome,” notes Beneo’s Sentko.

References:

1. NIH HMP Working Group et al. “The NIH Human Microbiome Project.” Genome Research, vol. 19, no. 12 (December 2009): 2317-2323
2. Fettweis JM et al. “The vaginal microbiome and preterm birth.” Nature Medicine, vol. 25, no. 6 (June 2019): 1012–1021
3. Lloyd-Price J et al. “Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.” Nature, vol. 569, no. 7758 (May 2019): 655–662
4. Dahlhamer JM et al. “Prevalence of inflammatory bowel disease among adults aged ≥18 years - United States, 2015.” Morbidity and Mortality Weekly Report, vol. 65, no. 42 (October 2016): 1166–1169
5. Proctor L. “Priorities for the next 10 years of human microbiome research.” Nature, vol. 569, no. 7758 (May 2019): 623-62
6. Lebeer et al. “Identification of probiotic effector molecules: present state and future perspectives.” Current Opinion in Biotechnology, vol. 49 (February 2018): 217-223