“In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system.”
Ok. So there’s mounting evidence that rapid colonization of the gut of neonates is important to immune development. Next step is to translate that into real medical therapies. There are immune and gut diseases that afflict newborns (also, in many cases, newborns are bombarded by antibiotics at this crucial time) – what have we learned to make them healthier and also ensure that their immune system develops properly?
via PLoS ONE: Patterns of Early Gut Colonization Shape Future Immune Responses of the Host.
“Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that, in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma compared to specific pathogen-free (SPF) mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.”
That’s the abtract from the paper “Gut Microbes Keep Rare Immune Cells in Line” (I think subscription is required, sorry).
There have been a good series of papers and studies into the “hygiene hypothesis” – that exposure to microbes early in life are actually important for the proper evolution of the immune system. This paper is one more example of that – these researchers were able to show what happened to the immune cells in the but of mice that never acquire bacteria, acquire bacteria only as adults, or acquire bacteria as pups.
I sometimes think of the 1850s-1990s as the Pasteurian Age – we were controlling bacteria to create a sterile world based on germ theory, aseptic techniques, public policies, and, of course, antibiotics. Alas, in the past 20 years, we’ve come to the realizations that we’ve reached (to joke a bit here) “peak antibiotics”, and that the only bugs to survive our clean homes and hospitals and antibiotics were Superbugs.
Now, in the past 5-10 years, I feel we are entering a post-Pasteurian Age, where we are gaining a deeper respect for the bacteria and fungi that share our world (and bodies) and that we are slowly thinking of how we can balance the sterile world we want and the microbe-filled world we need.
Great time to be a practical microbiologist, don’t you think?
“The results also showed that (i) consumption of an FMP containing five bacterial strains was not associated with a statistically significant change in the proportional representation of resident community members within and between individuals; (ii) the appearance and disappearance of strains comprising the FMP consortium did not exhibit familial patterns in the fecal microbiota; and (iii) B. animalis subsp. lactis CNCM I-2494 was the most prominent assayed member of the consortium represented in the microbiota during the 7-week period of FMP The results also showed that (i) consumption of an FMP containing five bacterial strains was not associated with a statistically significant change in the proportional representation of resident community members within and between individuals; (ii) the appearance and disappearance of strains comprising the FMP consortium did not exhibit familial patterns in the fecal microbiota; and (iii) B. animalis subsp. lactis CNCM I-2494 was the most prominent assayed member of the consortium represented in the microbiota during the 7-week period of FMP consumption. Analyses of the fecal gene repertoire over the course of the 16 weeks of the experiment indicated that (i) variations in the functional features of the (fecal) microbiome were less than the variations in bacterial species composition; (ii) there was no significant difference in the degree of similarity in representation of KEGG orthology group functions for a given co-twin at each time point compared to the degree of similarity that existed between co-twins, whereas individual and twin pair microbiomes were significantly more similar to one another than those from unrelated individuals; and (iii) there were no statistically significant changes in the representation of these functions when the FMP strain consortium was being consumed.”
This is a seminal paper in probiotic research. I have seen a ton of papers on this subject, but none were as thorough as this one. The one concern I had was that there was no control for the FMP (fermented milk product) matrix (I don’t know what to call it, but the fermented milk without the bacteria). I still think there might be a positive effect on the gut microbiome from that matrix.
But, these folks saw similar effects in humans who ate FMP and the mice who had only the bacteria that were found in the FMP, effectively showing what the effect of just the bacteria have on the microbiome.
Still, I’m curious to settle once and for all if there is any beneficial effect of the FMP matrix. My main thought here is that 1) we know that the lactose digesting bacteria help in the stomach (as seen in folks with lactose intolerance), but 2) only one bacterial species from the FMP really seems to make it all the way through the gut. Perhaps the matrix helps the microbiome or signals the microbiome to do something? In this study, it was suggested that the bacteria alone are activating specific microbiome metabolic pathway.
Fascinating stuff. Will need to dig into it more. And I just saw that there are some videos of the authors. Should be interesting.
via The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins. (subscription required, unfortunately).
What do you think of this work?
Indeed, Sharp said at the meeting, patients who come to Cleveland Clinic for treatment of inflammatory bowel disease express their own concerns about such approaches, which could include the use of probiotics, the consumption of live microorganisms, to treat intestinal and other maladies. “Many patients are worried about manipulating their gut microbiota,” Sharp said, adding that “they see these kinds of studies through the lens of genetically modified foods. They worry that tampering with the gut microbiome could lead to irreversible effects.”Sharp also urged the microbiome research community, along with funding agencies, to start doing more public outreach to counter the often “grossly misleading” statements made by companies that sell probiotic products, including claims that probiotics can cure cancers and treat autism spectrum disorders. “Most of what people know about this area of research comes from these retailers,” Sharp said. “We should not be relying on these companies to put out the first messages about this area of research.”
This is an interesting article on what’s next for human microbiome research. It lists some of the companies getting involved (great!) and some talk about what will happen to jumpt start a whole new round of funding.
What was surprising to me was how little money was put into the multi-year programs (total $167M). Prehaps I don’t have a feel for what’s a lot of money in research.
Read International Human Microbe Program Looks Ahead – ScienceInsider.
“Bacterial clone-based genome sequencing frequently results in gaps, which harbour hypothetical genes of unknown function. Sorek and colleagues show that these gaps contain a vast array of genes encoding proteins that are toxic to the sequencing host (Escherichia coli), including previously uncharacterized restriction enzymes, toxin–antitoxin systems and non-coding RNAs.”
Of course, to me, this is very clever, having never thought about this. Yes, we always knew that some sequences were unclonable because of incompatibility with the cloning vector. But the cleverness is to actually look for those gaps as potential anti micribials. That’s one of those amazing “Duh”s that sometimes happen when things are right under our nose.
Only sucky thing is that the article is CLOSED ACCESS. Fail.
via Access : Bacterial genomics: A new source of antimicrobial targets : Nature Reviews Microbiology (subscription required).
“Clostridium difficile has emerged rapidly as the leading cause of antibiotic-associated diarrheal disease, with the temporal and geographical appearance of dominant PCR ribotypes. We have undertaken a breadth genotyping study using multilocus sequence typing (MLST) analysis of 385 C. difficile strains from diverse sources by host (human, animal and food), geographical locations (North America, Europe and Australia) and PCR ribotypes. Results identified 18 novel sequence types (STs) and 3 new allele sequences and confirmed the presence of five distinct clonal lineages generally associated with outbreaks of C. difficile infection in humans.”
A broad survey to understand the nature of this pesky and increasingly common pathogen.
Read this article…
“Patterns of homologous gene flow among genomes of 12 strains from a single hot spring in Kamchatka, Russia, demonstrate higher levels of gene flow within than between two persistent, coexisting groups, demonstrating that these microorganisms fit the biological species concept. Furthermore, rates of gene flow between two species are decreasing over time in a manner consistent with incipient speciation.”
This is a really cool paper analyzing speciation in action. It shows how microbes slowly become less likely to swap genetic information as they differentiate. A key concept, too, is that each species has its own genetic island.
Great stuff.
Read this article…
“This study demonstrates that the milk-feeding type and the HLA-DQ genotype differently influence the bacterial colonization pattern of the newborn intestine during the first 4 months of life and, therefore, could also influence the risk of developing CD in later life. Breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder.”
Interesting study doing two things: 1) showing an effect of genotype on bacterial populations in the gut – and that they are different for those at risk for celiac disease; and, 2) showing a difference between the bacterial populations of breast-fed and formula-fed children, and a possible microbial reason why breast-feeding protects against celiac disease.
Very cool. And scary how it makes such good sense.
Read this article in PLoS ONE.
“We report on the remarkable degree of biodiversity in the wine yeast populations naturally present in a small area of Sicily where traditional (non-industrial) winery practices are still in place. Out of more than 900 yeast isolates recovered from late spontaneous fermentations, we detected at least 209 strains. Given that the characteristics of the wines produced were found to be industrially appealing, the study demonstrated the economic potential of preserving the patrimony of Sicilian yeast biodiversity and highlighted the importance of maintaining traditional wine making practices.”
This is a great paper – studying the biodiversity of yeast obtained from traditional wineries; analyzing their genetic and metabolic qualities; and even using a few to make wines.
How fun. How inspiring.
Read this article in PLoS ONE
UPDATE 15mar12: Science wrote a nice review on this article. Ironic though that a publication with closed access articles is writing about an open access article.
“For decades, Robert Daum has studied the havoc wreaked by methicillin-resistant Staphylococcus aureus. Now he thinks he can stop it for good.”
 Excellent story of the fight against MRSA by the guy who first made us aware of it.
Read this article…
Image from Nature
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