ITS 2012 Report – Nutrition and gut immunity – Are we eating the enemy?

by Maria Dalby – It is possible to modulate the body’s immune system by altering the gut microbiota, simply by changing the diet. Naturally occurring anti-inflammatory molecules, which are produced as by-products when bacteria in the large intestine digest vegetable matter, have been shown to attenuate systemic inflammation and inhibit autoimmune pathomechanisms. Dr Kendle Maslowski from Switzerland, who has published extensively in the area of immunology and gut microbiology, suggested that monitoring and manipulation of the human gut microbiota using available and novel pre- and probiotics may be a feasible alternative to developing new pharmacological treatments.

The human large intestine is home to a population of trillions of bacteria, from early infancy and throughout its entire life. There are, in fact, more bacteria living in the human gut than there are cells in the human body. These bacteria have co-evolved with their hosts into a vast metabolic factory that supply a range of essential nutrients that the human body cannot produce on its own. In addition, the gut microbiota also protects the body against infection by displacing pathogens and yeasts, and over the generations, both parties have developed specific mechanisms to promote this mutually beneficial relationship.

The composition of the gut microbiome is determined by the diet first and foremost – the gut flora of a herbivorous animal will differ considerably from that of a carnivorous predator or an omnivore.¹ At the same time, alterations of the human gut flora have been associated with a number of chronic conditions including asthma, rheumatoid arthritis, and type 1 and 2 diabetes, which has led scientists including Dr Maslowski to hypothesise that the gut flora may hold a clue to the increased incidence of these conditions in countries with a predominantly Western diet.

Of the many potentially immunomodulatory molecules produced by the human gut microbiota, the short-chain fatty acids (SCFA) acetate, propionate and butyrate have to date attracted the most interest in this field of research. These small compounds are produced during anaerobic bacterial fermentation of dietary fibre, mainly in the ascending colon. Patients with inflammatory bowel disease (IBD) have been shown to have reduced levels of SCFA, and supplementing SCFA through a high-fibre diet has been shown to have beneficial effects in conditions such as ulcerative colitis and bacterial enteritis. Acetate especially can reach high levels in serum; acetate binds to a G-protein coupled receptor called GPR43 which is highly expressed on innate immune cells. Studies in GPR43 knock-out mice have shown that these are more susceptible to acute and chronic colitis and to exacerbated peripheral inflammations in joints and airways. Tissue biopsies showed that acetate therapy reverses the inflammation in wild-type mice but not GPR43 knock-out mice [2]. Based on these findings, Dr Maslowski suggested that probiotics that promote acetate production, such as bifidobacteria strains, may be suitable candidates for restoring the symbiotic relationship between the gut microbiome and its host and normalise immune homeostasis, and that this in turn may enable further research into more advanced immune modulation via these mechanisms.

Kendle M Maslowski, University of Lausanne, Switzerland

References:

1. Ley RE, et al. Science 2008; 320 (5883): 1647-1651
2. Maslowski KM, et al. Nature 2009; 461 (7268): 1282-1286