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Calcified Tissue International (2018) 102:385–386
https://doi.org/10.1007/s00223-018-0391-7
EDITORIAL
Microbiota and Bone Health: The Gut-Musculoskeletal Axis
René Rizzoli
1
Received: 7 January 2018 / Accepted: 11 January 2018 / Published online: 9 February 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
The largest number of cells (10
E
14) in the human body are
located within the intestinal tract lumen. This number is
much higher than the number of cells in any human body
parenchyma. The estimated number of different species
varies between 1000 and 5000 comprising gram-positive
and gram-negative bacteria, Archaea, Eukarya, as well as
viruses. These organisms are collectively called the gut
microbiota (GM). They mostly refer to the large intestine
content, but all parts of the gastrointestinal tract are colo-
nized with an increasing density from the duodenum to the
distal colon. GM is now considered as an organ modulating
the expression of genes involved in mucosal barrier func-
tion, immune system, food digestion, and energy metabolism
[1]. The microbiome refers to the aggregate collection of
genomes and genes present in gut microbiota. Dysbiosis is a
state of microbial imbalance in the gut. It refers to a change
in microbiota structure and/or function [2]. Gnotobiotic ani-
mals are animals raised under germ-free conditions or under
germ-free conditions and then colonized with well-defined
and controlled microbes.
Gut microbiota can vary according to age [3], sex, diet,
living conditions [4], diseases requiring antibiotics treatment
[5], and drugs [6]. Over the last 12 years, GM has gathered
increasing interest because of associations or even causal
relationships as suggested or demonstrated for a large variety
of disorders including bowel inflammatory diseases, irrita-
ble bowel syndrome, colo-rectal cancer, obesity, metabolic
syndrome, type 2 diabetes, atherosclerosis, non-alcoholic
fatty liver, malnutrition, asthma, autoimmune diseases, pso-
riasis, multiple sclerosis, infections, anxiety, depression, and
autism. A link with GM has also been recognized for peri-
odontitis, rheumatoid arthritis, and spondyloarthropathies.
Bone homeostasis has also been shown to be influenced by
GM composition or production [7, 8]. In this special issue
of the Journal, the associations between bone health and GM
are reviewed and discussed.
In a well-detailed paper, Schwarzer and Strigini et al.
are reviewing the role of GM in growth, through experi-
mental models including Drosophila, worms, crustacea,
Zebrafish, chicken, and mice [9]. One factor implicated in
bone growth is insulin-like growth factor I (IGF-I). GM
is able to modulate and stimulate IGF-I synthesis by the
host in a dynamic interaction, as summarized by Yan and
Charles [10]. A GM–host interaction contributes to con-
trol the host immune system development. A series of
GM-produced factors influence immune cells, suggesting
a link between dysbiosis and autoimmune, metabolic, and
degenerative disorders as reviewed by d’Amelio and Sassi
[11]. By modulating the immune system, GM is becoming a
new player in the regulators of bone turnover and function.
Considering the interplay between bone physiology, gas-
trointestinal tract content, microbiology, and immunology,
Ohlsson and Sjögren are proposing the term “Osteomicro-
biology” to cover this field where GM changes are capable
of preventing ovariectomy-induced bone loss [12]. Such a
cross-talk appears to exist between GM and skeletal muscle
too. Grosicki et al. are summarizing the evidence for a role
of GM in the age-related changes in skeletal muscle mass,
structure, and function [13]. GM composition, metabolism,
and production can be modified by either prebiotics, which
are non-digestible fibers metabolized in the distal part of the
gastrointestinal tract, or probiotics, which are micro-organ-
isms conferring a health benefit on the host when admin-
istered in adequate amounts. These topics are extensively
discussed in two specific reviews [14, 15]. Finally, a pos-
sible source of both prebiotics and probiotics is fermented
dairy products, which in addition provide calcium, protein,
phosphorus, and various micronutrients. Their role in bone
growth and in age-related bone loss is summarized in the last
article of this special issue [16].
Gut microbiota appears to be a major player in the vari-
ous determinants of musculoskeletal health. However, it
remains to be demonstrated in well-conducted long-term
randomized controlled trials, whether interventions changing
* René Rizzoli
rene.rizzoli@unige.ch
1
Service of Bone Diseases, Geneva University Hospitals
and Faculty of Medicine, 1211 Geneva 14, Switzerland
@Phil_Robichaud
@deepthiw
@JoseServera