ECLESIASTES

No podemos abordar sistemas complejos con

herramientas lineales sin tener en cuenta la totalidad (un
martillo es muy útil para clavar un clavo, pero
absolutamente inútil para reparar el sistema operativo
de mi computadora). Podemos utilizar herramientas
lineales, pero, en el contexto de la complejidad. Es
fundamental el cambio de paradigma, un verdadero
salto epistémico, hacia la complejidad, el caos y la
incerteza. Donde todo puede “ser o funcionar de otra
manera”, donde los protagonistas (molécula-receptor,
por ej.) se modifican, a veces de modo antinómico de
acuerdo a las circunstancias contextuales
TANTO EL SISTEMA NERVIOSO
COMO EL CUERPO SE COMUNICAN
A TRAVÉS DE DISTINTO TIPO DE
SEÑALES QUE POR MECANISMOS
DE TRANSDUCCIÓN VAN
GENERANDO UNA ESPECIE DE
“LENGUAJE MULTINIVEL”.
Las moléculas en sí mismas “son
portadoras” y además, “son el
mensaje” que va generando una
conversación cruzada entre los
distintos sistemas que interactúan en
una determinada inter-fase. Ello
provoca cambios, transformaciones o
mantiene la estabilidad, según sea el
plan trazado.
It is becoming increasingly evident that peripheral organ-centered inflammatory
diseases, including chronic inflammatory liver diseases, are associated with
changes in central neural transmission that result in alterations in behavior. These
behavioral changes include sickness behaviors, such as fatigue, cognitive
dysfunction, mood disorders, and sleep disturbances. While such behaviors have a
significant impact on quality of life, the changes within the brain and the
communication pathways between the liver and the brain that give rise to changes
in central neural activity are not fully understood. Traditionally, neural and
humoral communication pathways have been described, with the three cytokines
TNFα, IL-1β, and IL-6 receiving the most attention in mediating communication
between the periphery and the brain, in the setting of peripheral inflammation.
However, more recently, we described an immune-mediated communication
pathway in experimentally induced liver inflammation whereby, in response to
activation of resident immune cells in the brain (i.e., the microglia), peripheral
circulating monocytes transmigrate into the brain, leading to development of
sickness behaviors. These signaling pathways drive changes in behavior by
altering central neurotransmitter systems. Specifically, changes in serotonergic
and corticotropin-releasing hormone neurotransmission have been demonstrated
and implicated in liver inflammation-associated sickness behaviors. Understanding
how the liver communicates with the brain in the setting of chronic inflammatory
liver diseases will help delineate novel therapeutic targets that can reduce the
burden of symptoms in patients with liver disease.
Secretin, originally isolated from upper intestinal
mucosal extract, is present throughout the
hypothalamo–neurohypophysial axis and that it
is released from the posterior pituitary under
plasma hyperosmolality conditions. In the
hypothalamus, it stimulates vasopressin
expression and release. Considering these
findings together with our previous findings that
show a direct effect of secretin on renal water
reabsorption, we propose here that secretin
works at multiple levels in the hypothalamus,
pituitary, and kidney to regulate water
homeostasis.
 Las neuronas entéricas liberan cinco
neurotransmisores: acetilcolina,
norepirefrina, óxido nítrico, péptido
intestinal vasoactivo y
serotonina. Éste último es producido
por las células enterocromafines que
tapizan el epitelio gastrointestinal.
En 1999 Michael Gershon publica su libro “El Segundo
Cerebro”, en el cuál plantea que el sistema digestivo y el
cerebro se encuentran en una constante comunicación .

Emeran Mayer, un importante investigador del eje tracto

digestivo-cerebro, afirma: “La comunicación cerebro-
tracto digestivo está firmemente establecida: si estas
estresado sentiras los efectos en tu intestino, si estas
ansioso te percataras de mariposas en tu estómago y si
estas deprimido, puedes desarrollar constipación “
Comunidades microbianas contribuyen en varios
procesos fisiológicos a través de la vida.
Una comunicación sexualmente dimorfica ocurre entre el
microbioma intestinal y el cerebro en paralelo con
cambios inmunitarios, metabólicos y neurológicos, lo
cuál sugiere que transiciones sexo-específicas que
deben ser considerados en estado de salud-enfermedad.

Jasarevic E, Morrison KE, & Bale TL. Sex differences in the gut microbiome-brain
axis across the lifespan. Philos Trans R Soc Lond B Biol Sci. 2016;
371(1688):20150122. doi:10.1098/rstb.2015.01 22.
Durante el período posnatal, a colonización microbiana
puede influenciar las diferencias sexuales en la
maduración de las células inmunocompetentes y el
funcionamiento del cerebro.
Perturbaciones ambientales, tales como el estrés
durante períodos críticos de desarrollo influencian la
señalización intestino-cerebro y estan ligados a la
reprogramación del eje intestino-cerebro de la
descendencia.
Las diferencias sexuales en la microbiota aparecen en la
adolescencia y continuan hasta la adultez
En la adultez, la microbiota intestinal es más estable y
aparece mejor adaptada a los desafios ambientales.
Es interesante observar, que el sexo puede configurar un
riesgo de síntomas negativos para la salud intestinal. En
realidad, desviaciones asociadas al género ocurren en la
autoinmunidad influenciados por a microbiota. Por
ejemplo, cambios sexo-específicos en la fisiología y
composición de la microbiota intestinal, pueden explicar
por lo menos en parte, el mayor riesgo de alergias y
enfermedades autoinmunes en las mujeres.
Estos investigadores encontraron que los pacientes con Trastorno
Depresivo Mayor presentaban alteraciones en la microbiota
relacionandolos con controles sanos.
Se observó una menor diversidad microbiana en estos pacientes,
caracterizada por alteraciones relativas en la phyla Firmicutes,
Actinobacteria y Bacteroidetes.
Cuando transplantaban la microbiota de pacientes con TDM en
ratones libres de gérmenes, estos desarrollaban síntomas
depresivos.

Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like

behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry. 2016;
1-11. doi: 10.1038/mp.2016.44
the absence of the gut microbiota
exacerbates the hypothalamic pituitary
adrenal (HPA) system reactivity to stress
and alters the anxiety-like behaviour
Microbial colonization of mammals is an
evolution-driven process that modulate
host physiology, many of which are
associated with immunity and nutrient
intake. Here, we report that colonization by
gut microbiota impacts mammalian brain
development and subsequent adult
behavior.
The functional development of the
mammalian brain is of particular interest
because it has been shown to be
susceptible to both internal and external
environmental cues during perinatal life.
Epidemiological studies have indicated an
association between common
neurodevelopmental disorders, such as
autism and schizophrenia, and microbial
pathogen infections during the perinatal
period
Gut microbiota regulates intestinal and
extraintestinal homeostasis. Accumulating
evidence suggests that the gut microbiota
may also regulate brain function and
behavior. Results from animal models
indicate that disturbances in the
composition and functionality of some
microbiota members are associated with
neurophysiological disorders,
strengthening the idea of a microbiota–gut–
brain axis and the role of microbiota as a
“peacekeeper” in the brain health
“The “normal” gut
microbiota is an integral part
of the external
environmental signals that
modulate brain development
and function”
 Los microorganismos realizan actividades
colectivas,(tipo conductas sociales),
intercambiando información (se comunican) y
formando asociaciones compuestas por muchas
células individuales (“sistemas biosociales”).
La coordinación celular en varios sistemas
“microbianos biosociales”, depende del contacto
químico y las interacciones físicas
Oleskina AV, El’-Registanb GI, Shenderov BA. Role of Neuromediators in the
Functioning of the Human Microbiota: “Business Talks” among
Microorganisms and the Microbiota-Host Dialogue. Microbiology 2016;
85(1): 1-22
La evidencia sugiere un rol importante de los
neuromediadores en la comunicación microbial.
Se han detectado desde catecolaminas a oxido
nítrico en las poblaciones de la microbiota.
Estas comunicaciones de las poblaciones de
microbiota tienen efectos mensurables en la
función cerebral.
En el futuro esta información podría ser utilizada
en el desarrollo de nuevos probióticos que
presenten un efecto neuroquímico específico
The discovery that the gut microbiota regulates
the neuroendocrine and behavioural responses
to stress paves the way for the hypothesis that
gut microbiota dysbioses could contribute to the
pathophysiology of anxiety-related disorders. In
this regard, treatments of anxiety-prone rodent
strains with probiotics or antibiotics aimed at
modifying their gut microbiota have shown an
anxiolytic-like activity. Clinical trials are now
needed to know if results obtained in preclinical
studies can translate to humans
Investigaciones actuales apoyan la idea de que las
comunidades microbiales en el intestino pueden jugar un
rol importante en la Salud Mental.
Nuevos estudios son necesarios en esta área a los fines
de dilucidar cuales serían las personas que se
beneficiarían con la suplementación con probíóticos, a
los fines de mejorar su funcionamiento mental.
Pirbaglou M, de Souza RJ, Stearns JC, Motamed M, Ritvo P. Probiotic
supplementation can positively affect anxiety and depressive symptoms:
a systematic review of randomized controlled trials. Nutr Res. 2016,
doi:10.1016/j.nutres.2016.06.009.
Wang H, Lee IS, Braun C, Enck P. Effect of probiotics on central nervous
system functions in animals and humans – a systematic review. J
Neurogastroenterol Motil. 2016, doi: 10.5056/jnm16018.
Few human studies assessing the effect of probiotic
supplementation on mental health through
modulation of brain-gut pathways have been
conducted to date. However, a recent systematic
review of 38 randomized controlled trials in both
animals and humans (25 were in animals, 15 in
humans and 2 studies were conducted in humans
and animals), led by Prof. Paul Enck from the
Department of Psychosomatic Medicine and
Psychotherapy at University Hospital Tübingen in
Tübingen (Germany), has concluded that probiotics
could be effective in improving psychiatric disease-
associated functions and memory abilities.
The paper by Wang, et al. found probiotics
that showed efficacy in improving
psychiatric disorder-related behaviours
(anxiety, depression, mood, stress
response) and memory
abilities (including spatial and non-spatial
memory) included Bifidobacterium (B.
longum, B. breve, and B. infantis) and
Lactobacillus (L. helveticus, L. rhamnosus,
L. plantarum, and L. casei).
 Although translations of animal studies to
human studies suggest possibilities, further
studies are worthwhile, especially in
patients with mental diseases that usually
show gastrointestinal comorbidities. In
addition to behavioural measurements such
as psychological questionnaires or scales,
more neuroimaging studies in humans are
needed in order to study what area is
altered in the brain that causes behavioural
changes after the consumption of
probiotics.
It has been previously suggested that a high-fibre diet can prevent
neurodegeneration by increasing gut microbiota derived butyrate in the
colon, but how changes in gut bacteria could influence brain development
and function is still poorly studied.
A recent study, led by Dr. Mauro Costa-Mattioli from the Baylor College of
Medicine in Houston, Texas (USA), has found that the reintroduction of a
commensal bacterial strain can reverse asocial behaviours in mice that are
seen in autism spectrum disorders (ASDs).

Buffington SA, Di Prisco GV, Auchtung TA, et al. Microbial reconstitution reverses maternal diet-induced social and synaptic
deficits in offspring. Cell. 2016; 165(7):1762-75. doi:10.1016/j.cell.2016.06.001.
Santocchi E, Guiducci L, Fulceri F, et al. Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial
on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry. 2016; 16:183.
doi:10.1186/s12888-016-0887-5.