1
Gut Microbiome and Inflammatory Bowel Disease
Bidirectional brain-gut interactions are highly relevant in human intestinal diseases
such as irritable bowel syndrome (IBS), and preclinical studies help shed light on
its complexity. Dysbiosis of the bacterial gut microbiome became apparent and microbiome
modulation is now considered an important target for treatment. To study the pathology
of IBS, Wouter J. de Jonge (Amsterdam, The Netherlands) and colleagues employed animal
models for stressful early life events that are known to predispose to IBS at adult
age. Transplantation of microbiota from a visceral hypersensitive rat to a normosensitive
one transferred the phenotype, suggesting that the microbiome is critical in the stress-induced
hypersensitivity. Furthermore, the authors addressed potential mechanisms by which
neural signals can affect host defense and microbiome composition in the gut lumen.
T lymphocytes were found to be very responsive to neuronal signals; and genetic knockout
studies have revealed a critical function of these T cells in regulating anti-microbial
peptides by intestinal epithelia. As such, the effect of stress and neuronal activity
could relay to host defense mechanisms of the gut epithelia and microbial richness
and diversity. Future studies are warranted in the field of microbiome adaptation
for IBS pathology.
2
Modulation of Gut Microbiota in Obesity and Cardiometabolic Disorders
Changes in gut microbiota are associated with metabolic disorders such as obesity,
type 2 diabetes and cardiovascular risk factors. Patrice D. Cani (Brussels, Belgium),
Willem M. de Vos (Wageningen, The Netherlands) and collaborators have identified Akkermansia
muciniphila as a potential target to treat cardiometabolic disorders and inflammation.
A. muciniphila is a mucin-degrading bacterium living in the gut's mucus layer. The
authors demonstrated that feeding mice with A. muciniphila reduced bodyweight, fat
mass and inflammation, and restored gut barrier function by acting on mucus layer
thickness and restoring the production of antimicrobial proteins. The authors also
showed that in obese people, the abundance of A. muciniphila was inversely related
to fasting plasma glucose levels, visceral fat accumulation and adipocyte diameter
in subcutaneous adipose tissue. Upon caloric restriction, obese individuals with higher
baseline A. muciniphila showed improved insulin sensitivity markers and other cardiometabolic
risk factors. In summary, strategies to modulate A. muciniphila composition in the
human gut to treat obesity and cardiometabolic disorders warrant further investigation.
3
Liver Diseases and Gut Microbiota
The hepatic portal vein conducts blood from the gastrointestinal tract to the liver,
carrying metabolites produced by the gut microbiota making the liver one of the main
organ that can be influenced by microbiome composition and activities. Philippe Gérard
(Jouy-en-Josas, France) and collaborators demonstrated that a specific dysbiosis in
intestinal microbiota (IM) was associated with alcoholic liver disease (ALD) severity
in patients. The researchers transplanted germ-free and conventional mice with human
IM from alcoholic patients with or without alcoholic hepatitis (AH). Mice receiving
IM from an AH patient developed more severe liver inflammation with an increased number
of liver T and NK lymphocyte subsets, higher liver necrosis, greater intestinal permeability
and higher translocation of bacteria than mice harboring the IM from an alcoholic
patient without AH (noAH). Distinct differences in IM composition could be observed,
with key deleterious bacterial species being associated with AH and the Faecalibacterium
genus being associated with noAH. A subsequent transfer of IM from a noAH patient
could improve alcohol-induced liver lesions in conventional mice previously transplanted
with IM from an AH patient. In conclusion, it may be possible to prevent and manage
ALD by IM manipulation.
4
Gut Microbiota in Cystic Fibrosis
Fiona Fouhy (Fermoy, Ireland) and colleagues in the CFMATTERS project presented novel
longitudinal data on the cystic fibrosis (CF) gut microbiota. The researchers examined
the gut microbiota of individuals with CF at stability, during pulmonary exacerbation
and post exacerbation, and compared that to non-CF controls. DNA was extracted from
fecal samples and the 16S rRNA gene was sequenced on the Illumina MiSeq platform.
During exacerbation, changes in microbiota at phylum, family and genus levels were
detected before intravenous antibiotic therapy, but the most dramatic changes in microbiota
were seen after therapy commencement. Functionality of the gut microbiota was also
interrogated using samples from 6 people with CF and 6 controls, with shotgun metagenomic
sequencing and metabolomic analysis. Pathways involved in lipid metabolism and xenobiotic
degradation increased in the CF group compared to the controls. Metabolites were also
altered. This study highlights temporal changes in CF gut microbiota, metabolites
and microbiota functionality.
5
Skin Microbiota in Health and Disease
While the gut microbiota is intensively investigated, knowledge about the skin microbiota,
its protective function and immunomodulatory properties remains limited. The skin
microbiota of the face and upper back is dominated by Staphylococcus and Propionibacterium
species; in particular, Propionibacterium acnes predominately colonizes sebaceous
areas. Using comparative genomics analysis, Holger Brüggemann (Aarhus, Denmark) and
colleagues revealed the multi-phyletic composition of P. acne; certain P. acnes phylotypes
are associated with healthy skin while others are associated with skin disorders such
as acne vulgaris and progressive macular hypomelanosis. Confocal microscopy revealed
the colonization pattern of P. acnes within the lumen of sebaceous follicles; healthy
skin contained an organized, biofilm-like network of bacteria that does not seem to
get in close contact with the adjacent keratinocyte layer. In contrast, in acne-affected
skin, P. acnes was found to be tightly associated to skin cells, which might lead
to the activation of innate immune responses. The data highlighted the fragile balance
between P. acnes and the skin microenvironment, and a dysbiosis in P. acnes phylotype
composition may lead to skin disorders.
6
Skin and Hair Aging, Lifestyle and the Skin and Scalp Microbiomes
William W. Mohn (Vancouver, Canada) reported on a cross-sectional study investigating
the skin and scalp microbiome in relation to skin and hair aging and lifestyle, and
involving 495 subjects 10–78 years of age. Diversity of the scalp microbiome increased
with age, but its overall composition was not correlated with age. The reverse was
true of the forehead microbiome. The authors also showed that specific microbial populations
were correlated with visible signs of skin and hair aging and lifestyle factors. Many
forehead populations were associated with age and, more weakly, with age-related characteristics
like periorbital wrinkling and facial hyperpigmentation, while the reverse was true
for scalp populations. Overall, facial skin and scalp have distinct microbiome communities
uniquely associated with skin and hair aging and lifestyle factors. Two Corynebacterium
populations exhibited a striking pattern of co-exclusion on both the forehead and
scalp. One population was abundant on most subjects in younger age classes, but it
appeared to be completely displaced by the other during middle age.