Developments surrounding our understanding of the intestine and it’s associated microflora are contending to be the most exciting research topics of the decade. Almost
weekly cutting-edge research emerges in this arena, furthering our understanding behind the involvement of the “gut and the intestinal microflora” in health maintenance or disease promotion.
In the last week alone more than five great major research journals have published phenomenal ‘special editions’ dedicated to the intestinal microflora.
Harvard’s Richard Blumberg discusses how advances in the Human Microbiome Project may offer insights into the causes behind the obesity epidemic.
Obesity and insulin resistance worldwide have traditionally been explained by the host’s intake of higher calorific Western-style diets
He goes on say that the tides are turning to include the impact the the 100 trillion plus microbes have calorie extraction.
Along these lines, the June 2012 editions of Nature and PLoS ONE have published an update on the “Human Microbiome Project (HMP). The goal of this 5+ year, $173 million dollar ongoing study is to better understand our fellow travelers. More than 80 universities and science institutions are participating in the specimen from 18 different body sites from 300 or more healthy subjects.
Key findings so far:
100 Trillion microbes occupy the human terrain
10 times the number of cells 1-3% of body weight
More than 10,000 microbial species
Human genome encodes for 22,000 protein-coding genes
Microbiome contributes some 8 million protein-coding genes
360 times more genetic material
Similarly last week Science and Science Translational Medicine joined forces to update their 2005 review series“Gut: The Inner Tube of Life.” As the name “The Gut Microbiota” implies, this updated 2012 edition features 15 great articles from top-notch researchers in human microbiology, including my personal favorites Jeffrey Gordon, Peter Turnbaugh, Lora Hooper and Kristen L. Mueller, among others.Below are quick summaries from two great articles from this review that you should check out.
Nicholson et al discuss in “Host-Gut Microbiota Metabolic Interactions” the important links between gut microbiota and development of the human intestinal immune system, starting at birth. Following birth is the parallel, “co-creation” of both the founder gut microflora and the gastrointestinal immune system. Imbalances during this developmental period such as birthing method, antibiotic exposure and early life food choices have lifelong heath implications, says Nicholson et al.
“Events early in life, such as delivery mode, maternal pre-pregnancy body mass index, and antibiotic treatment during infancy, influence obesity in later childhood…” Nicholson et al 2012.
Lora Hooper discusses advances in the “Interactions Between the Microbiota and the Immune System,” with a particular focus on host tolerance. The intestinal immune system “Toll-erates” the massive microbial organ through two means:
1) minimizing contact
2) confining penetrating bacteria to specific intestinal immune sites, such as the gastrointestinal lymphoid tissue or GALT.
Hooper et all term this process “Inside-out control” for dendritic cell (DC) sampling compartmentalizes any translocated microflora to the GALT and minimizes contact through secretion of anti-microbial peptides such as IgA. This process is contingent upon proper gut barrier and tight junction function, notes Lora.
Moreover, the microbial-immune cross-talk is a two way street. Commensal microbiota shape T differentiation of cell subsets and are capable of influencing adaptive immunity via triggering increased production of immune suppressive Treg cells, locally inside the gut and systemically.
Last but not least, yet another special issue dedicated to the intestinal microbiota appeared in the July 2012 edition of Clinical Microbiology and Infection (CMI). This multi-publication review series titled “Microbiome: Deciphering the last human body organ,” features a collection of reports from the 18th annual Spanish Scientific Symposium.
Stanford researchers Macrobal et al discuss the power of breast milk in the context of influencing intestinal microflora colonization during early infant life. The steady decline of intestinal oxygen levels during the first few months of life favor the colonization of anaerobic species from the Bifidobacterium, Bacteroides and Clostridium genera. It turns out human breast milk is the perfect microbial fertilizer. Containing more than 200 different oligosaccharides, human breast milk preferentially supports the growth of species belonging to Bifidobacterium and Bacteroides.
“…. consumption of breast milk influences the microbial landscape of the infant gut….beneficial effects in the gut and contribute to the well-being of the newborn.” Marcobal et al 2012
My personal favorite researcher Dr. Cani discusses the communication system linking the intestinal microflora with inflammation and obesity. Dr. Cani proposes that the low grade inflammation characteristic to both obesity and type 2 diabetes originates in the gut. In 2007, Dr. Cani’s group was the first to demonstrate that “obesogenic diet” induces a domino effect in the intestine culminating in inflammation-associated insulin resistance and adipose tissue excess. Increased fat intake causes a transient shift in the microbial ecology of the intestine, and a concomitant decline in gut barrier function. The above processes facilitate enhanced intestinal absorption of bacterial-derived endotoxins leading to ‘metabolic endotoxemia.’ after the increased presence of Gram-negative bacterial Lipopolysaccharides (LPS) in the serum of obese and insulin resistant individuals.
Dr. Cani discusses the application of prebiotics in the context of both intestinal-endotoxin neutralization and enhancing the production of gut-peptides with known metabolic and intestinal barrier restorative effects- namely glucagon-like peptide 1 and 2, or GLP-1 and GLP-2, respectively.
Another mechanism that Dr. Cani discusses at length is how intestinal microbial components can promote increased adipose tissue formation via activation of the the cannabinoid system, which has been shown elsewhere to be increased in obesity. Dr. Cani’s novel finding adds a twist to our previous understand of the cannabinoid in the context of obesity. The intestinal cannabinoid system known as the endocannabinoid (eCB), is too activated by high-fat diets and intestinal endotoxin. Similarly, Cani et al have found that administration of inulin-type prebiotics reduces endocannabinoid system tone through a endoxotin-dependent mechanism, thereby favoring improvements in fat and liver cell lipid load.
Many of these themes discussed above will be explored during the 2012 Abelson Symposium “Microbiomes and 21st Century Medicine”, organized by AAAS/Science and Science Translational Medicine. This cutting edge symposium will bring together leading scientists to discuss what we know and don’t know about the ecology, metabolism and immunology of the gut microbiome and the roadblocks to translating this knowledge into strategies to combat disease and improve human health worldwide.
(Cani 2012) Cani, P. D. Crosstalk between the gut microbiota and the endocannabinoid system: impact on the gut barrier function and the adipose tissue. Clinical Microbiology and Infection 2012; 18: 50–53. doi:10.1111/j.1469-0691.2012.03866.x
(Marcobal 2012) Marcobal, A., & Sonnenburg, J. L. Human milk oligosaccharide consumption by intestinal microbiota. Clinical Microbiology and Infection 2012; 18, 12–15. do:10.1111/j.1469-0691.2012.03863.x
(Nicholson 2012) Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012). Host-Gut Microbiota Metabolic Interactions. Science, 336(6086), 1262–1267. doi:10.1126/science.1223813
Patrice Cani (2012). Crosstalk between the gut microbiota and the endocannabinoid system: impact on the gut barrier function and the adipose tissue Clinical Microbiology and Infection , 18, 50-53 DOI: 10.1111/j.1469-0691.2012.03866.x