Helicobacter pylori genome found in the stomach of a 5300-year-old Ice man

Oetzi the Iceman

Oetzi the Iceman was found in 1991 in the high Oetzal Alps that span Italy and Austria.  He is a mummy who gained popularity in the scientific community because of how well he was preserved and thus the potential to provide a glimpse into Europe’s past (he is thought to be around 5,300 years old, alive in the European Copper Age).  Many studies have examined his diet, health, and genetics, but recently researchers were able to discover identify and examine his stomach and intestines.  Biopsy samples were collected and PCR analysis determined the presence of the gram-negative bacteria Helicobacter pylori. 

H. pylori can be found in about half of the world’s population, and while research has pointed to the harmful effects of this bacterial strain, recent work has supported that the bacteria can in fact protect against some illness such as acid reflux and asthma.  However, extensive characterizing Oetzi Iceman’s H. pylori could also shed light on ancient human migration patterns.  Specifically, modern strains of H. pylori are assigned to distinct populations based on their geographical heritage, originating from either ancestral Asian populations (AE1) or hybrids between North Africa and Europe (AE2). 

Comparative whole genome analysis showed that Oetzi Iceman’s H. pylori genome has highest similarity to three apAsia2 H. pylori genomes from India, and further high-resolution analysis of ancestral motifs revealed a co-ancestral matrix, showing that H. pylori shares ancestry with Indian strains but also with most European strains.  Low levels of H. pylori ancestry was shared with the AE2 ancestry, which was interesting to scientists as it suggests AE2 introgression into Europe after the Copper Age.  This was later than what has been proposed previously by the scientific community.  Ultimately, these findings showed that Oetzi Iceman had H. pylori with strong AE1 genetic Asian origins, suggesting that the AE2 bacteria from African heritage began arriving after the Copper Age of European civilization.  

The microbiome affects celiac severity in mice

In non-celiac people, gluten is broken down into its constituent proteins and does not elicit any immune response.  In celiac disease, however, the gluten proteins cause inflammation, which can result in a number of GI issues.  The microbiome has long been thought to play a role in this disease, because of its importance to immune mediation, and its role in gluten breakdown.  An international group of scientists recently tested the role of various different characteristic microbiome communities on the immune reaction in mice with celiac disease.  They published their results last week in the American Journal of Pathology.

The scientists used a mouse model for celiac disease that involved genetically modified mice that had an immune response to gluten.  They split the mice into three groups, one group had a typical healthy microbiome, the next had a healthy microbiome but without proteobacteria, and the final group was germ free (i.e. completely lacking a microbiome).  When the germ free mice were challenged with gluten they had the highest inflammatory response.  This included increases in immune cells, and breakdown of the intestinal villi.  Unsurprisingly, when the germ free mice were colonized with normal microbiota, their inflammatory response was attenuated.   The scientists then discovered an important relationship between celiac’s and Proteobacteria.  The mice that harbored this phylum had more severe responses to gluten, suggesting that these bacteria somehow worsen the inflammatory response to gluten.  Antibiotic treatment that increased the amounts Proteobacteria, and the relative abundances of Escherichia, Helicobacter, Pasteurella, and Lactobacillus, also increased the inflammatory response.

The exact mechanisms by which the microbiome are mediating the immune response are unclear.  Bacteria are known to induce various immune cells and also break down gluten, and these mechanisms may be involved.  In either case gluten sensitivity and celiac disease are clearly affected by the microbiome.