Research News

Are clues about childhood asthma and heightened immune responses found in a baby’s gut microbiome?

Thursday, 27 October 2016 09:27

It is well known that gut microbiota in early life is linked to several immune-related diseases. It has been previously reported that during the first 100 days of life there is a window where microbe-based diagnostics and therapeutics may be useful to prevent the development of asthma in high-risk individuals.

A recent study, led by Prof. Susan Lynch from the Division of Gastroenterology at the Department of Medicine at University of California in San Francisco (California, USA), has found that neonatal gut microbiome dysbiosis may predict later atopy and asthma development in childhood.

By studying stool samples (n=298; aged 1-11 months) through 16S ribosomal ribonucleic acid (rRNA) sequencing from a United States birth cohort, neonates (median age 35 days) were divisible into three microbiota composition states (1: the lowest risk group; 2: the medium risk group, and 3: the highest risk group) representing three different risk groups. Neonatal gut microbiotas exhibited significantly different relative risk (RR) of predominantly multisensitized (PM) atopy development at age 2 years and of parental report of doctor-diagnosed asthma at age 4 years. PM atopy at age 2 years was defined using a statistical algorithm that clusters subjects according to their pattern of serum specific-immunoglobulin E responses to a panel of ten food and aeroallergens. The highest risk group (group 3) showed lower relative abundance of certain bacteria (including Bifidobacterium, Lactobacillus, Akkermansia and Faecalibacterium), higher relative abundance of particular fungi (Candida and Rhodotorula) and a distinct faecal metabolome enriched for pro-inflammatory metabolites, when compared to either of the lower-risk groups (groups 1 and 2). Neonatal gut dysbiosis in the highest risk group was consistent with previously described early-life (3 months of age) gut microbiota taxonomic depletions that increase infants’ risk of asthma. These data suggest that neonatal gut microbiota dysbiosis is characteristic of PM atopy and asthma development in later childhood.

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Hints that composition and diversity of gut bacteria could impact progression of Alzheimer’s disease

Thursday, 27 October 2016 09:21

Alzheimer’s disease (AD) is the most common form of incurable dementia. On a cellular level, AD is characterized by the accumulation of extracellular aggregates of the amyloid-b peptide or Ab plaques (named amyloidosis) and intracellular aggregates of tau protein or neurofibrillary tangles in certain brain regions. Neuro-inflammation, or inflammation of the microglia (the brain’s macrophages), is also a consistent hallmark of the disease.

A recent review suggests that the peptide Ab associated with AD may have antimicrobial functions via a new pathway that involves trapping invading microorganisms, including bacteria (such as Salmonella enterica), fungi (such as Candida albicans), viruses (such as herpes simplex virus) and parasites (such as Toxoplasma gondii). One preliminary theory holds that AD could be linked to brain infection, which the generalized innate immune response fails to control and thus may lead to Ab plaque accumulation that cannot be effectively cleared by microglia. In the aged AD brain, the protective function of Ab fails and it has been suggested that other risk factors beyond infection are involved. A healthy gut microbiota could contribute to preventing systemic infection by limiting pathogen growth, maintaining barrier function, and training the host immune system. The reviewed data provide evidence for the role of microorganisms in neurodegenerative diseases such as AD.

However, the exact molecular mechanisms and causal chain of events leading to AD remain elusive. Given the role for gut microbes in modulating host immunity and brain function through the microbiota-gut-brain axis, recent research interest has focused on studying the role of intestinal microbiota composition in regulating neuro-inflammation in AD.

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How do bacteria affect the brain at different life stages?

Thursday, 27 October 2016 09:16

Growing evidence (at least from mouse models) suggests gut bacterial composition in early life can have effects on the brain; at the Harvard Symposium, Tracy Bale of University of Pennsylvania (USA) detailed her work showing that exposing mice to stress in early pregnancy changes their vaginal microbiome and induces similar-looking changes in the offspring’s gut microbiota at birth. These changes may alter the brain, for example, by reprogramming the young mouse’s hypothalamus, with various effects on behaviour. Bale also noted that the effects of early prenatal stress in mice are greater and more persistent in males, raising the question of whether there could be sex-specific interventions to offset these effects.

Later came the opposite end of the lifespan: in the example of Parkinson’s disease, gut microbiota may also exert effects. Filip Scheperjans of Helsinki University Hospital (Finland) presented a talk on Parkinson’s disease and the slowly growing number of studies that link it to gut microbiota compositional differences. He described three studies showing dysbiosis in Parkinson’s disease, but noted that the nature of the dysbiosis was different from study to study. Further research is required to find out whether probiotic interventions could improve motor symptoms themselves, or only the gastrointestinal symptoms (e.g. constipation) associated with the condition.

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What are humans’ earliest microbial exposures?

Thursday, 27 October 2016 09:12

Physicians and researchers have long thought babies in the womb were sterile and that their first microbial exposures occurred during birth. At the symposium, Kjersti Aagaard of Baylor College of Medicine (USA) walked the audience through the growing evidence that microbial exposure starts before birth. Aagaard says her lab, and now seven others, have found evidence of culturable bacteria in the placenta. She noted that the placenta constitutes a microbially sparse habitat compared with other body sites—its bacterial load lies somewhere between a hot tub and the New York subway.

Aagaard showed data suggesting the microbiome of neonatal meconium varies according to the mother’s diet during gestation—namely, her fat intake. This connection underscores the importance of maintaining an appropriate diet and a healthy microbial community during pregnancy.

Josef Neu of University of Florida (USA) continued the theme of early microbial exposure by talking about microbes in the guts of infants who are breastfed. Neu mentioned the advantages of breastmilk for the developing infant and noted that a baby’s microbial dose from human milk is similar to the dose used in some probiotics studies. He predicted that in the future, mothers who cannot breastfeed may have access to more advanced products that approximate breastmilk: potentially beneficial microbes could be added to pasteurized donor milk, for example.

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