Maternal vaginal and gut microbial populations may influence offspring
behavior, physiology, and/or neuropathology. These influences may either
be indirect due to changes in maternal behavior or direct due to
microbial product exposure. Studies on the sterility of the mammalian
placenta and amniotic fluid are controversial. Administration of
antibiotics during gestation induces hypo activity, anxiety-like
behavior, locomotion and social deficits in offspring. ASD-like
mannerisms including social deficits and repetitive behavior in
offspring are caused by maternal high fat diets. Cross-fostering
offspring with surrogate conventional dams or administration of the
probiotic, Lactobacillus reuteri, reverses these
mannerisms(Bercik et al. 2011). Maternal microbial metabolites,
fermentation products and bacterial structural components like
lipopolysaccharides (LPS) and peptidoglycan (PG) can cross the placenta.
Fetal brains exposed to PG or LPS present with anxiety-like behaviors
and cognitive deficits. Prenatal infections, particularly febrile
infections, procure significantly higher risks of schizophrenia and ASD
in humans. Offspring of maternal immune activation (MIA) mice models,
generated by administration of LPS which induces fever during gestation,
display decreased cognitive function and anxiety-like behaviors(Foley et
al. 2014). Administration of Bacteroides fragilis lowers
intestinal barrier permeability and decreases microbial metabolite
concentrations which normalizes these behaviors. Postnatal neurogenesis,
including migration, differentiation, apoptosis and synaptic pruning of
glial cells, continues over a lifespan(Foley et al. 2014). Hippocampal
neurogenesis reduction from long-term antibiotic treatment causes a
reduction in novel object recognition. Exercise and the administration
of probiotics corrects these anomalies. The gut microbiome mediates gut
and brain serotonergic pathways; whereas, serotonin is known to support
postnatal neurogenesis(Möhle et al. 2016). Antibiotic treatment augments
myelin related transcripts in the prefrontal cortex but cannot be
reversed by the transplantation of SPF GM into GF mice(Gacias et al.
2016).
Test 1
Early life microbiome perturbations can have lifelong metabolic,
physiological and immunological implications. Vaginal birth ensures that
maternal vaginal microbiota species particularly Lactobacillus
and Prevotella will colonize offspring which confers protection.
Exposure to prenatal stress adversely changes vaginal microbiomes.
However, probiotics taken by the mother during gestation can transfer to
the offspring during vaginal birth. Infants born by cesarean section
have higher risks of autoimmune disease because they are initially
colonized by skin residing bacteria, such as Staphylococcus and
Corynebacterium . Exposing these neonates to their mother’s
vaginal microbiota can partially remedy this mishap. In rats, short-term
antibiotic therapy that partially depletes microbiota has no effect on
anxious or depressive-like behaviors but visceral hypersensitivity
presents in adulthood(Koenig et al. 2011; Jašarević et al. 2015). Short
term antibiotic therapy temporarily decreases anxiety-like behavior in
adult mice but returns in two weeks after the microbiota resumes their
normal composition. Postnatal long-term broad spectrum antibiotic
therapy permanently reconstitutes host microbial profiles and functions
which then modify brain chemistry and behavior. Specific conditions can
be altered, reversed or prevented by transient and/or permanent
colonization of probiotics. Probiotics can beneficially reduce
repetitive, anxiety and depressive-like behaviors as well as stress in
animal models. Probiotics also promote communication, proper cognitive
functioning and social behavior in animals. Humans given a probiotic
containing fermented milk product twice a day for a month show less
reactive emotional responses to images of distressed faces than
controls. Microbiota-gut-brain communication is said to be
bidirectional. GM can affect their host and a host can affect its
GM(Bailey et al. 2011; Gacias et al. 2016). Early life stressors, such
as separation from maternal mothers in mice, induce differences in
microbial composition which then produce anxiety-like behaviors.
Presence of a single bacterial species or microbial consortiums may
initiate depressive-like behaviors in their host.
If adult hosts maintain steady diets, lifestyles, health and
geographical residency, then their microbiome’s diversity and
composition remain in relative temporal equilibrium. High microbial
diversity is positively correlated with redundant health and the absence
of disease(Lloyd-Price et al. 2016). GM are linked to neurodevelopmental
and neurodegenerative disorders whereas gastrointestinal comorbidities
and food allergies are commonly found in ASD, depressive and elderly
patients. GM are also linked to stress related disorders in humans such
as IBD. GM are also linked to stress induced anxiety-like behaviors in
rodent models(de Theije et al. 2014). ASD patients show consistent
variances in species richness and diversity, especially in
Clostridia species. The following differences are found in ASD
patients versus controls: close associations of Sutterella with
intestinal epithelium, absence of the probiotic Prevotella as
well as elevations in non-spore forming anaerobes and micro aerophilic
bacteria. The following differences are found in schizophrenic patients
versus controls: presence of a Lactobacillus specific phage, high
abundances of oropharyngeal residing Lactobacillus, as well as
high diversity alpha and beta species in the blood(De Angelis et al.
2013). Declines in microglial function associated with brain
inflammation often precede depression. The antibacterial minocycline
acts as an antidepressant in humans. Minocycline inhibits microglia.
Major depressive disorder (MDD) patients have higher abundances of
Actinobacteria and lower abundances of Bacteroidetes than
controls. GF mice exhibit depressive-like behavior after transplantation
of MDD patient GM samples(Molina-Hernández et al. 2008; Miyaoka et al.
2012).
As the ENS degenerates with age, the microbiome loses resilience and
reflects shifting bacterial taxa prevailing Firmicutes to
dominant Bacteroidetes. Elderly microbiomes, when living in the
community, more closely simulate young adults than when living in care
facilities. Supplementation of the probiotic, Lactobacillus rhamnosus
GG, elevates SCFA levels which tips GM composition towards
anti-inflammatory exhibiting taxa(Eloe-Fadrosh et al. 2015).
Patients with neurodegenerative diseases have abnormal microbial
populations. AD patients have decreases in Allobaculum and
Akkermansia as well as increases in Rikenellaceae compared to
controls. PD patients exhibit lower concentrations of
Prevotellaceae and SFCA as well as higher concentrations of
Lactobacilliaceae and tissue associated Escherichia coli.
Tremor dominant PD are distinguished from postural and gate dominant PD
patients by lower rates of Enterobacteracea (Harach et al. 2015;
Hasegawa et al. 2015). Microglia functioning and
neuro-inflammation account for the inhibition and advancement
neurodegenerative disease. SFCA produced by microbiota encourages
microglial maturation and supports microglial maintenance(Unger et al.
2016). MAMPs that mimic host molecules and enter brain tissue cause low
level inflammation. Amyloid pathogenic plaques in AD patients act as
brain associated antibacterial agents. The autoimmune condition uveitis
occurrs in an immune privileged site and is mediated by auto reactive T
cells also capable of recognizing gut associated microbial
antigens(Kumar et al. 2016).
Rates of neurophysiological disorders are increasing more than ever.
Perhaps microbiomes are being forced to adapt to human and environmental
changes at a speed that is nonsynchronous with rates required for
symbiotic coevolution. Questions remain regarding the interplay between
host associated microorganisms and the brain. Do microbiomes or the host
conditions initiate disorders? Are these single or cumulative changes
beneficial or pathogenic to the host? Is GM dysbiosis a causative or
correlating factor in host dysbiosis? Does GM produce, promote or
exacerbate clinical symptoms? Does GM affect the host directly via
microbial metabolites or indirectly via immune system modification? Are
single bacterial species or accumulations of bacterial consortia
responsible for host symptoms?
Data extrapolated from animal models may not be applicable to humans.
Population studies may not be relevant to individuals. Collective
generations of host genetics, diets, geographical residence, lifestyle
furthermore eating, drinking, sleeping and exercising habits accumulate
to shape an individual’s microbiome. GM that cause disease in one
patient, such as obesity, can be beneficial to a kwashiorkor patient.
Full genomic and metabolic analyses of both host and microbiome may be
an inexpensive option for patients soon. Future diagnoses may involve a
GF mouse and an SPF mouse being treated with the following processes:
host fecal transplantation, short-term antibiotic administration,
long-term antibiotic treatment and systematic probiotic administration.
Future treatments may be customized and tailored to the individual’s
personal standards of health.
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