Antibodies derived from mom's gut microbes

Research in mice shows antibodies derived from mom's gut microbes protect newborns from E. coli infection

Science Daily/January 8, 2020

Harvard Medical School

Newborn mice derive protective antibodies from their mothers' microbiota. Antibodies derived from mothers' microbiota ward off both localized and widespread systemic infections by the bacterium E. coli. Study points to the role of maternal microbes in offspring protection and neonatal immunity. Findings can inform development of microbe-based therapies against infectious diarrhea in infants.

Mother's milk has been long touted for its salutary effects on the newborn and its ability to shield infants from certain infections.

Now research from Harvard Medical School conducted in mice shows that at least part of its protective effects come from a surprising source: the microbes residing in maternal intestines.

The new study, published Jan. 8 in Nature, shows that antibodies made in response to one particular organism in the maternal gut are passed on to the offspring both via milk and through the placenta to protect newborn pups from infection by at least one disease-causing, and potentially lethal, microbe, E. coli.

The findings add to a growing body of evidence pointing to the potent role of the microbiota -- the trillions of microbes that dwell in the gut, skin, mouth and other parts of the bodies of mammals, including humans -- in disease and health.

But the new research goes a step further -- it specifically identifies maternal microbiota as source of newborn immunity. It further suggests that the intestinal microbiota could offer immune protection even when mothers have had no prior encounters with an infection that allows them to build and pass on protective antibodies to their offspring.

"Our results help explain why newborns are protected from certain disease-causing microbes despite their underdeveloped immune systems and lack of prior encounters with these microbes," said study senior investigator Dennis Kasper, professor of immunology in the Blavatnik Institute at Harvard Medical School. "Moreover, they raise the possibility that mothers can confer immune protection to their offspring even to pathogens that they haven't themselves encountered in the past."

If affirmed through further studies, the findings could inform the design of microbial therapies against dangerous infections such as E. coli and other disease-causing organisms, the researchers said.

"Albeit preliminary, we are hopeful these insights could inform the development of vaccines derived from commensal microbial molecules as a way to prevent infectious diseases," said Kasper, who is also the William Ellery Channing Professor of Medicine at Brigham and Women's Hospital. "Another therapeutic avenue could be the use of commensal microbes as probiotics that protect against diarrheal disease."

Infectious diarrhea -- most commonly due to E. coli or rotavirus -- is the leading cause of malnutrition and the second leading cause of death globally in children under age 5. It causes 1.7 billion infections and claims more than 520,000 lives a year worldwide, according to the World Health Organization.

Without any prior exposure to microbes, a newborn's immune system is a blank slate. For the first three weeks, a newborn's immune protection is derived entirely from maternal antibodies passed onto the fetus during pregnancy via the placenta, during birth via the birth canal, and shortly after birth via breastfeeding.

In the current study, researchers worked with newborn mice genetically engineered to lack B cells -- the antibody-producing factories of the immune system. Some of the newborn mice were subsequently raised by mothers that were also born without antibody-making B cells, and therefore, lacked protective antibodies. The other newborn mice were raised by mothers that had normal immune systems.

Mice exposed to protective antibodies from their mothers were far more resistant to E. coli infection than mice that were not exposed to such antibodies. It was as if the pups repelled the pathogen, the researchers observed. Indeed, their intestines had 33 times fewer E. coli bacteria than newborn mice lacking maternal antibodies. By contrast, mice pups that were not exposed to protective antibodies developed disseminated E. coli disease.

The researchers were also able to pinpoint the specific organism responsible for inducing the formation of the protective antibodies -- a microbe called Pantoea, member of the Enterobacteriaceae bacterial family, which resides in the intestines of mice and other mammals, including humans.

Furthermore, the experiments showed that the antibodies enter both the intestines and bloodstream of newborns via the neonatal Fc receptor, a molecular channel on the placenta that helps ferry protective antibodies from the mother to the growing fetus. Thus far, the receptor has been known to transfer antibodies through the placenta. However, the experiments conducted in the new study show this receptor also absorbs antibodies derived from milk and ferries them from the intestines and into the bloodstream of the newborn mice, ensuring wider, systemic protection beyond the gut. Adult mice, in which this neonatal receptor loses its function with age, did not transfer protective antibodies from their gut to the bloodstream, the experiments showed.

https://www.sciencedaily.com/releases/2020/01/200108131659.htm

'Ridiculously healthy' elderly have the same gut microbiome as healthy 30-year-olds

October 11, 2017

Science Daily/University of Western Ontario

In one of the largest microbiota studies conducted in humans, researchers have shown a potential link between healthy aging and a healthy gut.

With the establishment of the China-Canada Institute, the researchers studied the gut bacteria in a cohort of more than 1,000 Chinese individuals in a variety of age-ranges from 3 to over 100 years-old who were self-selected to be extremely healthy with no known health issues and no family history of disease. The results showed a direct correlation between health and the microbes in the intestine.

"The aim is to bring novel microbiome diagnostic systems to populations, then use food and probiotics to try and improve biomarkers of health," said Gregor Reid, professor at Western's Schulich School of Medicine & Dentistry and Scientist at Lawson Health Research Institute. "It begs the question -- if you can stay active and eat well, will you age better, or is healthy ageing predicated by the bacteria in your gut?"

The study, published this month in the journal mSphere, showed that the overall microbiota composition of the healthy elderly group was similar to that of people decades younger, and that the gut microbiota differed little between individuals from the ages of 30 to over 100.

"The main conclusion is that if you are ridiculously healthy and 90 years old, your gut microbiota is not that different from a healthy 30 year old in the same population," said Greg Gloor, the principal investigator on the study and also a professor at Western's Schulich School of Medicine & Dentistry and Scientist at Lawson Health Research Institute. Whether this is cause or effect is unknown, but the study authors point out that it is the diversity of the gut microbiota that remained the same through their study group.

"This demonstrates that maintaining diversity of your gut as you age is a biomarker of healthy aging, just like low-cholesterol is a biomarker of a healthy circulatory system," Gloor said. The researchers suggest that resetting an elderly microbiota to that of a 30-year-old might help promote health.

"By studying healthy people, we hope to know what we are striving for when people get sick," said Reid.

The study also found a distinct anomaly in the group aged 19 to 24 that has not been observed in large-scale analyses of other populations and they suspect may be unique to this healthy cohort in China. The distinct gut microbiota of this group was a surprising finding and requires further study.

https://www.sciencedaily.com/releases/2017/10/171011123728.htm

Stress during pregnancy related to infant gut microbiota

January 26, 2015

Science Daily/Radboud University

Women who experience stress during pregnancy are likely to have babies with a poor mix of intestinal microbiota and with a higher incidence of intestinal problems and allergic reactions. This could be related to psychological and physical problems as the child develops.

Stress during pregnancy is often linked to physical and psychological problems in the child. But why is this? Could the infant's gut microbiota be an underlying mechanism? An initial study of the correlation in humans has shown that babies born to mothers who experience stress have a poorer mix of intestinal microbiota.

For the purposes of this study, the stress and anxiety levels of pregnant women were measured by means of questionnaires and testing the levels of the hormone cortisol in saliva. In addition, faeces samples from 56 babies were tested from 7 days until 4 months after birth. A correlation was found between the mothers who reported high stress levels and presented high cortisol levels and the variety of microbiota in the babies' guts, even when the analyses took breastfeeding and postnatal stress into account.

Different mix of bacteria

Mothers who reported high stress levels and presented high cortisol readings had babies with more Proteobacteria and fewer lactic acid bacteria and Actinobacteria in their microbiota. This represents a poor mix of microbiota, which was also reflected in the relationship between the presence of these microbiota and a higher incidence of intestinal problems and allergic reactions among the babies in this research group.

Mechanism

'We think that our results point towards a possible mechanism for health problems in children of mothers who experience stress during pregnancy. Giving other bacteria would probably benefit these children's development,' says Carolina de Weerth, professor of developmental psychology in the Behavioural Science Institute of Radboud University Nijmegen, and corresponding author of the article that is in press in Psychoneuroendocrinology.

http://www.sciencedaily.com/releases/2015/01/150126095425.htm

Prebiotics may help to cope with stress

Prebiotic fibers can help to protect beneficial gut bacteria and restore healthy sleep patterns after a stressful event

February 10, 2017

Science Daily/Frontiers

Probiotics are well known to benefit digestive health, but prebiotics are less well understood. Recent study in rats shows that prebiotic fibers may help to protect beneficial gut bacteria and restore healthy sleep patterns after a stressful event.

Probiotics are well known to benefit digestive health, but prebiotics are less well understood. Prebiotics are certain types of non-digestible fibers that probiotic bacteria feed on, such as the fibers found in many plant sources like asparagus, oatmeal, and legumes. Certain bacteria also feed on non-fibers such as the protein lactoferrin, which also acts like a prebiotic and is found in breast milk.

According to a new study published in the online journal, Frontiers in Behavioral Neuroscience by Professor Monika Fleshner, PhD, and her team from the University of Colorado, Boulder, regular intake of prebiotics may promote beneficial gut bacteria and recovery of normal sleep patterns after a stressful episode.

"Acute stress can disrupt the gut microbiome," explained Dr. Agnieszka Mika, a postdoctoral fellow and one of the authors of the study, "and we wanted to test if a diet rich in prebiotics would increase beneficial bacteria as well as protect gut microbes from stress-induced disruptions. We also wanted to look at the effects of prebiotics on the recovery of normal sleep patterns, since they tend to be disrupted after stressful events."

In this experiment, test rats received prebiotic diets for several weeks prior to a stressful test condition and compared with control rats that did not receive the prebiotic-enriched diet. Interestingly, rats that ate prebiotics prior to the stressful event did not experience stress-induced disruption in their gut microbiota, and also recovered healthier sleep patterns sooner than controls.

Given that these experiments were done in rats, are these results relevant for humans? "The stressor the rats received was the equivalent of a single intense acute stressful episode for humans, such as a car accident or the death of a loved one," said Dr. Robert S. Thompson, the lead author of the study. "A next set of studies will be looking exactly at that question -- can prebiotics help humans to protect and restore their gut microflora and recover normal sleep patterns after a traumatic event?"

In the mean time, should we start including prebiotics in our diets to help cope with stress? "So far no adverse effects from prebiotics have been reported," said Dr. Mika, "and they are found widely in many plants, even present in breast milk, and are already commercially available." Healthy gut bacteria and restful sleep could be your benefits.

https://www.sciencedaily.com/releases/2017/02/170210130951.htm