Inflammation and mood pathways
In this exciting area of research, one of the open questions
is how chronic inflammation might be initiated and maintained
in illnesses such as depression, and what the gut has
to do with this. Emerging studies show that the normally
very selective intestinal barrier may be compromised in
depression (and in numerous conditions where depression
is often a hallmark symptom) [49-56]. Psychological stress
and exhaustive exercise have been shown to increase the
permeability of the intestinal barrier [57-59]. However,
a Westernized diet high in fat and sugar has also been
shown to cause a more porous intestinal lining, the consequences
of which include systemic access to food antigens,
environmental toxins, and structural components of
microbes, such as lipopolysaccharide endotoxin (LPS)
[60]. The latter agent, LPS, is particularly important regarding
depression; even relatively small elevations in systemic
LPS levels have been shown to provoke depressive symptoms
and disturb blood glucose control [61-67]. Endotoxins
such as LPS can decrease the availability of tryptophan
and zinc, thereby negatively influencing neurotransmission
[68,69]. Moreover, systemic LPS can elevate inflammation
and oxidative stress. Traditional dietary practices have
completely divergent effects of blood LPS levels; significant
reductions (38%) have been noted after a one-month
adherence to a prudent (traditional) diet, while the
Western diet provokes LPS elevations [70]. These and
other findings help establish mechanisms whereby the
LPS-lowering, antioxidant, and anti-inflammatory properties
of broad traditional dietary practices, as well as specific
components within them, can help provide mood
support. Indeed, when the limitation of intestinal absorption
is overcome, individual phenolic structures have been
shown, at least experimentally, to curb the breakdown of
central neurotransmitters, mimicking the proposed mechanistic
properties of some primary antidepressant medications
[71,72]. As we will discuss, enhanced bioavailability
via fermentation may therefore be an important factor in
food (or herbs) as medicine.
Microbiota and mental health
Related to the differences in traditional versus contemporary
Westernized dietary patterns and mental health is the
role of the intestinal microbiota. A decade ago, prior to the
scientific hypotheses of Logan et al. [73,74], the notion that
the intentional manipulation of the intestinal microbiota
could provide therapeutic value to human depressive and
fatigue states was, at the very least, outlandish. However, in
the ensuing years, many of the mechanisms first proposed
by Logan and colleagues (as listed, adapted from [73,74])
whereby beneficial microbes could influence mood or
fatigue, have been examined experimentally.
Direct protection of the intestinal barrier;
Influence on local and systemic antioxidant status,
reduction in lipid peroxidation;
Direct, microbial-produced neurochemical production,
for example, gamma-aminobutyric acid (GABA);
Indirect influence on neurotransmitter or
neuropeptide production;
Prevention of stress-induced alterations to overall
intestinal microbiota;
Direct activation of neural pathways between gut
and brain;
Limitation of inflammatory cytokine production;
Modulation of neurotrophic chemicals, including
brain-derived neurotrophic factor;
Limitation of carbohydrate malabsorption;
Improvement of nutritional status, for example,
omega-3 fatty acids, minerals, dietary
phytochemicals;
Limitation of small intestinal bacterial overgrowth;
Reduction of amine or uremic toxin burden;
Limitation of gastric or intestinal pathogens
(for example, Helicobacter pylori);
Analgesic properties.
Moreover, preliminary placebo-controlled human studies
have shown that oral probiotic microbes can decrease
anxiety, diminish perceptions of stress, and improve
mental outlook [75]. In the context of our later discussion
of fermented foods and their intersection with the gutbrain-microbiota
connection, a brief summary of this
microbiota-brain research is necessary. For interested
readers, more detailed reviews specific to the scientific
advances exploring direct and indirect relationships
between intestinal microbes and anxiety or depression
have recently been published [76,77].
Viewed strictly from the nutritional perspective, experimental
studies have shown that the administration of probiotic
bacteria to laboratory chow can increase peripheral