Degradation of chemokines by food-borne bacterium

The diet, previous or ongoing encounters with infectious organisms and parasites as well as bacterial microflora that inhabit the intestinal tract or other mucosal surfaces – all these factors influence the quality of immune responses. To mention just one relevant case – in developing countries people appear to be less affected by autoimmune diseases but in wealthy societies autoimmunity represents the constantly growing problem. This phenomenon may be partially due to the much lower level of contact with parasitic worms in places where higher civilization level is attained. It has been shown that some parasites (Schistosoma mansoni is the best known example) seem to be able to exert the regulatory effect on mammalian immune responses and thereby reduce the risk of inappropriate reactions to self-antigens. The microflora may also be a factor in autoimmunity development. The publication I have found describes details of interactions between probiotic-associated bacterial molecule and pro-inflammatory chemokines many of which are involved in autoimmune diseases.

The link:

This report is a continuation of previous study where it has been shown that a cell surface protein from Lactobacillus casei strain derived from VSL#3 (a probiotic food product used in management of ulcerative colitis) can degrade IP-10 (interferon gamma induced protein 10, known also as CXCL10 – a pleiotropic pro-inflammatory chemokine). Authors use molecular biology techniques to prove that the described earlier protein is a serine protease. The action of this protease is not specific to IP-10 as it degrades a number of other chemokines (CXCL9, CXCL11, CXCL12, CX3CL1 and CCL11). On the other hand several well-known pro-inflammatory agents like RANTES, IL-6, IFNγ and TNF are not affected.

Investigators attempt to translate L.casei-dependent chemokine degradation into the physiological setting. To this end they use TNFΔARE/+ model (mice lacking post-transcriptional regulation of TNF that develop spontaneous inflammatory bowel disease). The intraperitoneal injections of L.casei-conditioned media reduces several pro-inflammatory parameters like ileal IP-10 level, activation of certain signaling pathways and infiltration of ileum by mononuclear cells or T cells. Authors proceed to screening fecal human samples for bacteria displaying similar abilities and identify microflora-derived L.casei strain that also degrades IP-10. This strain and its mutated version with the disrupted copy of gene encoding the protease in question are used to feed mice with intestinal inflammation (the different disease model is used this time – Rag2-/- mice that received IL-10 deficient CD4 T cells). The presence of L.casei with protease reduces cecal inflammation indices like IP-10 level or T cell influx whereas the protease-deficient strain is unable to influence the above parameters.

Such capacity of L.casei – the regulation of immune responses via degradation of potent pro-inflammatory agents has provoked me to hypothesize about the origin of dairy products consumption. The hypothesis I have is a tentative one and I am not sure whether it reflects the true reason-effect relationship. I am also aware that it drifts far away from the data presented in the discussed paper and I do not know if it has not has been already proposed by somebody else. Let me state few facts: (1) L.casei belongs to the bacterial group called LAB (lactic acid bacteria). LAB comprises species that are associated with mammalian mucosal surfaces and food products including milk (they are not limited to milk, however). (2) The human capacity to consume milk and dairy products beyond infancy period dates back to the time of agricultural revolution and the transition from hunter-gatherer lifestyle. Interestingly, genomic data indicate that the enzyme metabolizing milk lactose has undergone huge selection events which are comparable to the selection that in the recent human history affected factors responsible for skin pigmentation.

What was the true reason behind our ability to digest milk as adults? Could it be the presence of food-borne bacteria that were able to regulate mucosal immune responses? The transition to the agriculture had to involve many dramatic changes in human diet (most probably in human microbiota, too) and first farmers tended to be actually less healthy than hunters-gatherers (I need to indicate that I have no specialist knowledge of ethnography and I rely here on several general science books I have read – most notably Pandora’s Seed: Why the Hunter-Gatherer Holds the Key to Our Survival by Spencer Wells). Might the extended period of milk consumption be able to alleviate the stress on human physiology imparted by modifications to the original human lifestyle?

Such line of thinking brings another question. What could be special about the original human microbiome? The remaining hunter-gatherer people are distinctively free from diseases comprising so-called metabolic syndrome (source: The Cambridge Encyclopedia of Hunters and Gatherers). Might it be partially due to specific microbiota they harbour? The only relevant report I could find indicates that the oral microbiome of Batwa pygmies is significantly more diverse than in their agricultural neighbors (High diversity of the saliva microbiome in Batwa Pygmies: PLoS One. 2011; 6(8):e23352). Maybe we can find solutions to ever-increasing burdens of civilization in those vanishing people?

von Schillde MA, Hörmannsperger G, Weiher M, Alpert CA, Hahne H, Bäuerl C, van Huynegem K, Steidler L, Hrncir T, Pérez-Martínez G, Kuster B, Haller D. (2012). Lactocepin Secreted By Lactobacillus Exerts Anti-Inflammatory Effects By Selectively Degrading Proinflammatory Chemokines Cell Host&Microbe DOI: 10.1016/j.chom.2012.02.006


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