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Clinical & Translational Immunology (2016) 5, e107; doi:10.1038/cti.2016.61
Official journal of the Australasian Society for Immunology Inc.
www.nature.com/cti
EDITORIAL
The gut microbiota and immune-regulation: the fate
of health and disease
Clinical & Translational Immunology (2016) 5, e107; doi:10.1038/cti.2016.61; published online 2 November 2016
T
he gut microbiota is relevant to many diseases due to its direct
impact on the development and maintenance of the immune
system. Moreover, both the gut microbiota and the immune system
are intimately related to many other physiological processes such as
metabolism and behavior, as well as the digestive, respiratory and
nervous systems. The amount of information gained in the last 5 years
signifies the gut microbiota now as another important organ in our
body. With diseases such as obesity, stroke, cancer, depression and
autism increasing in prevalence, the debate centres upon whether
many diseases have a gut origin. The interplay between the intestinal
immune system, the epithelial barrier and the bacteria that resides
within, is fundamental to maintaining a healthy gut homeostasis and
determining the fate of health and disease. The host genetics and many
environmental factors such as diet, early exposition to antibiotics,
stress, drugs and many pollutants contribute to altering the balance
of good and bad bacteria (dysbiosis) in the gut, subsequently
compromising the gut permeability, often called ‘Leaky gut’. Many
inflammatory diseases are collectively being pinned on having a gut
wall that allows toxins and autoimmune triggers to escape from the
intestinal lumen leading to health problems. In this Special Feature
of Clinical & Translational Immunology, we share our insights into
the interplay between environmental factors, gut microbiota and
metabolites, and their effects on human development, inflammation,
infection, obesity, diabetes and chronic kidney disease. Likewise, we
briefly discuss the challenges and opportunities in gut microbiota
research and how novel therapeutic strategies targeting the gut
microbiota will be beneficial for humans.
The trillions of microbes that reside in our body and particularly in
our gastrointestinal tract, together with our genome, constitute a
complex dialogue. Vieira et al.1 explain how the gut microbiota
develops from birth and their interactions with the host become
critical for the formation of a healthy or a disease-promoting
microbiota. This review exposes the relevance of maternal diet and
breastfeeding on gut microbiota modulation from early to late stages
of life and the use of prebiotic, probiotic and postbiotic treatment, and
fecal microbiota transplantation.
The intense enthusiasm for research into the gut microbiota over
the past decade has resulted in a deeper understanding into how the
bacterial alteration of dietary components may have critical roles in
host health and disease. Our diet is one of the main environmental
factors that can dramatically affect the gut microbiota ecology.
Richards et al.2 illustrate that changes in lifestyle are more pronounced
in Western societies where the consumption of processed foods high
in fat and carbohydrates are important contributors to the worldwide
rates of obesity, autoimmune and inflammatory diseases such as type 1
and type 2 diabetes. In this review, Richards et al.2 explain that, from
fiber fermentation, gut microbiota produce high concentrations of
dietary metabolites or short-chain fatty acids (SCFAs) such as
acetate, propionate and butyrate that keep the gut healthy, but also
have beneficial anti-inflammatory effects. The reviews by Richards
et al.2 and Correa et al.3 describe a whole mechanistic process by
which the microbial SCFAs modulate the innate and adaptive immune
system. These articles describe how SCFAs are known to modify
several cellular processes including gene expression, chemotaxis,
differentiation, proliferation and apoptosis, and discuss the signaling
pathways such as activation through G-protein coupled receptors
(GPCRs) or inhibition of histone deacetylases (HDACs) as the possible
mechanisms of action.
Studies in both mice and humans are showing the impact of dietary
or host-derived metabolites on host metabolic processes such as
insulin resistance and diabetes as the leading causes for the
development of cardiovascular and chronic kidney disease (CKD).
Felizardo et al.4 discuss that the progression of CKD is strictly related
to changes in the composition of the gut microbiota and poorly
ingested fibre-enriched foods. More importantly, they explain how
microbial metabolites have an impact on advanced renal failure and
secretion of nitrogen compounds (urea, uric acid), which leads to the
influx and overgrowth of bacteria in the gastrointestinal tract that
correlates with the generation of uremic toxins. This Brazilian team
discusses whether CKD development is a consequence or cause of an
unhealthy gut microbiota—many lines of evidence supporting how
dysbiosis could be linked to the progression of kidney diseases.
The advances in understanding of diet–microbiota–host interactions
proposes significant possibilities to create new therapeutic strategies,
including re-engineering gut bacteria species to selectively alter the
microbial production of molecules to promote human health and
prevent disease. Lobo et al.5 reveal several studies on Bacteroides fragilis
and Polysaccharide A (PSA) as the first evidence of a symbiotic
bacterial molecule that coordinates anti-inflammatory responses
essential for the host’s health. More importantly, this review reminds
us that, although gut microbiota may have beneficial effects in health,
in cases where the epithelial barrier of the gut is breached, commensal
bacteria can escape the gut lumen, translocate to other organs and may
be involved in pathogenic processes. Lobo et al.5 describe this process
in inflammatory peritonitis and systemic sepsis. Interestingly, this
article reflects on the use of antibiotics that affect the gut microbiota
Editorial
2
composition/behaviour, which has never been taken into account
and could be one of the causes of the long-term latent health
complications.
Antibiotics are the result of many years of research focused on how
to eradicate pathogenic organisms in humans, which unfortunately
also harm the beneficial commensal gut microflora. In the past, studies
of non-pathogenic commensal bacteria were restricted because those
microbes were thought to have insignificant effects on human health
compared with pathogens. Nowadays, studies show that keeping the
gut microbiota healthy by boosting their diversity and composition
will be an alternative therapeutic approach to fight infections,
autoimmunity, cancer and many other inflammatory diseases. Moore
and Stanley6 presented the technologies that are currently used for
dissecting the gut microbiota. From 16S rRNA gene to shotgun
sequencing, these exciting technologies have tremendously increased
our knowledge about the role of the gut microbiota in health
and disease. Moreover, this review discusses the challenges in the
design and analysis for the characterization of the gut microbiota in
animal models and the implications at the time to extrapolate those
results to humans.
The gut microbiota that lives in mutual symbiosis in the human host
benefits from those dietary components highly resistant to digestion, as
a source of food. In turn, the human body benefits from essential
metabolites and vitamins produced by the gut microbiota, which also
helps us to harvest nutrients from food. The advanced knowledge in
the era of the gut microbiota brings new opportunities for personalized
medicine, which can have a high impact on previously established
targeted treatments and prevention of diseases. Moreover, the identification of how these bacterial species crosstalk with our immune
system and contribute to better health is of upmost significance.
CONFLICT OF INTEREST
The author declares no conflict of interest.
Clinical & Translational Immunology
Eliana Mariño
Monash Biomedicine Discovery Institute,
Immunity and Infection Division, Monash University,
Melbourne, Victoria, Australia
E-mail: [email protected]
1 Vieira AT, Fukumori C, Ferreira CM. New insights into therapeutic strategies
of gut microbiota modulation in inflammatory diseases. Clin Trans Immunol 2016;
5: e87.
2 Richards JL, Yap YA, McLeod KH, Mackay CR, Mariño E. Dietary metabolites and the
gut microbiota: an alternative approach to control inflammatory and autoimmune
diseases. Clin Trans Immunol 2016; 5: e82.
3 Corrêa RO, Fachi JL, Vieira A, Sato FT, Vinolo MAR. regulation of
immune cell function by short-chain fatty acids. Clin Trans Immunol 2016;
5: e73.
4 Ferreira Felizardo RJ, Castoldi A, Andrade-Oliveira V, Câmara NOS. microbiota
and chronic kidney diseases: a double-edged sword. Clin Trans Immunol 2016;
5: e86.
5 Lobo LA, Benjamim CF, Oliveira AC. The interplay between microbiota and
inflammation: lessons from peritonitis and sepsis. Clin Trans Immunol 2016;
5: e90.
6 Moore RJ, Stanley D. Experimental design considerations in microbiota/inflammation
studies. Clin Trans Immunol 2016; 5: e92.
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