Certain types of intestinal bacteria can help protect the liver from injuries such as alcohol or acetaminophen overdose, according to Emory scientists led by pathologist Andrew Neish and physiologist Dean Jones.
The research was published on March 25 in Cell Metabolism.
“The composition of the microbiota, because of natural variation, dysbiosis, or supplementation with probiotics, can strongly affect how the liver processes both toxins and pharmacological agents, and thus have clinical consequences on how individuals respond to such exogenous chemicals,” Neish says.
While pretreatment with bacteria is needed for the observed effect in acute liver injury, probiotics or small molecule substitutes may be useful in the treatment of chronic liver diseases, the authors suggest.
In mice, oral administration of Lactobacillus rhamnosus or LGG could protect against liver damage brought on by alcohol or acetaminophen. Several labs had already observed a beneficial effect from LGG against liver injury, but the Emory research establishes an additional mechanism.
The protection comes from a small molecule metabolite produced by the bacteria called 5-MIAA (5-methoxyindoleacetic acid), activating the mammalian transcription factor Nrf2. Other types of bacteria did not produce 5-MIAA or activate Nrf2. While LGG is also known to improve the barrier function of the gut and dampen inflammation, liver-specific depletion of Nrf2 prevented LGG’s beneficial effects, suggesting that this is the primary mechanism of action. Read more
Interest in bacteria and other creatures living on and inside us keeps climbing. On August 15 and 16, scientists from a wide array of disciplines will gather for the Emory Microbiome Research Center inaugural symposium.
On the first day, Lab Land is looking forward to hearing from several of the speakers, touching on topics stretching from insects/agricultural pathogens to neurodegenerative disease. The second day is a hands on workshop organized by instructor Anna Knight on sorting through microbiome data. The symposium will be at WHSCAB (Woodruff Health Sciences Center Auditorium). Registration before August 2 is encouraged!
Many of the projects that we highlighted four years ago, when Emory held its first microbiome symposium, have continued and gathered momentum. Guest keynotes are from Rodney Newberry from WUSTL and Gary Wu from Penn.
In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found.Â One oxygen-shy type of bacteria that grows in the wound-healing environment,Â Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal andÂ human obesity.
An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.
The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.
The results were published on January 27 inÂ Nature Microbiology.Â Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.
â€œThis is a situation resembling recovery after a forest fire,â€ says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. â€œOnce the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.â€ Read more
AÂ Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria â€“ lactobacilli â€“ activates the same ancient signaling pathway in intestinal cells in both insects and mammals.Â It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).
Asma Nusrat, MD
A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliverÂ that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.
This ideaÂ has advanced experimentally, as demonstrated byÂ twoÂ papers from Jones and Neishâ€™s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.
Nusrat told me Friday her team began investigatingÂ annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria areÂ activating the same molecular signals.Â (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)
In aÂ secondÂ Journal of Clinical Investigation paper published this February, NusratÂ and herÂ colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more
Guest post from Courtney St Clair Ardita, MMGÂ graduate studentÂ andÂ co-author of the paper described. Happy Halloween!
In the past, reactive oxygen species were viewed as harmful byproducts of breathing oxygen, something that aerobic organisms just have to cope with to survive. Not any more. Scientists have been finding situations in humans and animals where cells create reactive oxygen species (ROS) as signals that play important parts in keeping the body healthy.
One example is when commensal or good bacteria in the gut cause the cells that line the inside of the intestines to produce ROS. Here, ROS production helps repair wounds in the intestinal lining and keeps the environment in the gut healthy. This phenomenon is not unique to human intestines. It occurs in organisms as primitive as fruit flies and nematodes, so it could be an evolutionarily ancient response. Examples of deliberately created and beneficial ROS can also be found in plants, sea urchins and amoebas.
Researchers led by Emory pathologist Andrew Neish have taken these findings a step further and identified the cellular components responsible for producing ROS upon encountering bacteria. Postdoctoral fellow Rheinallt Jones is first author on the paper that was recently published in The EMBO Journal. Read more
While humans have been consuming fermented foods such as yogurt and kimchi for centuries, a visitor to a modern grocery store can see the recent commercial enthusiasm for adding probiotic bacteria to foods.Â A recent article inÂ SlateÂ explores the confusion over potential health benefits for these added bacteria.
The bacteria that live inside us seem to play an important role regulating metabolism, the immune system and the nervous system, but scientists have a lot to learn about how those interactions take place.
Researchers at Emory have been clarifying exactly how probiotic bacteria promote intestinal health. Andrew Neish and his colleagues have found that the bacteria give intestinal cells a little bit of oxidative stress, which is useful for promoting the healing of the intestinal lining.
Beneficial bacteria induce reactive oxygen species production by intestinal cells, which promotes wound healing.