Trenz Pruca

15 October 2021

Diet and Depression

While acknowledging the complex and multidirectional
nature of the relationship between diet and mental health,
we propose that diet is an essential part of a balanced
approach to combating depression. A large number of
promising studies have examined the relationship between
diet and depression. In particular, one study examined 16
eligible randomized controlled trials with outcome data for
more than 45,000 participants. The findings from this study
indicate that dietary intervention significantly reduced
depressive symptoms in high-quality trials (g = 0.321, 95%
CI = 0.12–0.53, p = 0.002) (122). Other meta analyses and
clinical studies have revealed an association between diet
quality and the probability of and risk for depression (123,
124). Additionally, pro-inflammatory dietary patterns have
specifically been linked to a greater likelihood of
developing depression and depressive symptoms in clinical
studies (125–127).
Eating patterns during the COVID pandemic showed an
increased adoption of unhealthy diets. A study by Robinson
et al., examining the impact of COVID-19 on a large
sample of UK adults (n = 2,002) during social lockdown
showed that 82% reported an increase in the intake of
unhealthy food (128). Furthermore, 36% of the participants
reported an increase in alcohol intake compared to before

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lockdown which is known to cause disruption of the gut

microbiome (129) by causing bacterial overgrowth (130,
131) and hyper-permeability of the intestinal membrane
(i.e., leaky gut) (132). In this regards, Pollard et al., also
reported an increase in alcohol intake of 14% over the
baseline in 2019 during the COVID-19 pandemic in a
sample that included 1,540 adults in the U.S. (133).
Studies have also established a relationship between the
prevalence of depressive symptoms and certain eating
habits. For example, depressive symptoms have been
associated with a high glycemic index attributed to a high
intake of sugars and refined carbohydrates (126, 127, 134).
Conversely, healthy eating habits that limit sugar intake and
refined carbohydrates are associated with a decreased risk
of depression. Such findings align with several smaller and
more recent trials where considerable improvements in
depression levels were observed in people who followed the
so-called “Mediterranean Diet” (135–137). For context, the
Mediterranean diet, which adheres to healthy eating
practices, is associated with a small intake of red meat; a
high intake of vegetables, fruits, beans, and nuts; and a
medium intake of eggs, dairy, and poultry (123, 126, 127).
We propose that the consistently significant and positive
effects of dietary intervention on depressive symptoms
reflect the impact that diet has on the microbiome. While
recognizing the role that genetics and antibiotics play, we
believe that diet is a potentially adjustable determining
factor of the relative abundance, diversity, and functionality
of organisms comprising the gut microbiome. In the same
vein, no single treatment is likely to fully ameliorate

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depression and/or depressive symptoms, in fact, combined

therapeutic approaches (a holistic approach) may include
several areas including pharmacological interventions,
psychiatric therapy and lifestyle and nutritional changes.
For example, studies have shown that the artificial
sweetener Splenda™ promotes gut dysbiosis and the
increased growth of Proteobacteria, which is an indicator
for inflammation (138). Additionally, decreased function of
the gut barrier, also known as “leaky gut,” is linked to an
“unhealthy” gut microbiome that is attributed to a diet high
in saturated fats, refined sugars, artificial sweeteners, and
low in fiber, aka the “Western” diet (125, 139, 140). On the
other hand, a diet high in fibers, polyphenols (flavonoids
and phenolic acid micronutrients found in berries, nuts,
flaxseeds, vegetables, olives, coffee, and tea) and
unsaturated fatty acids (fatty acids that have one or more
carbon-carbon double bonds, comprised of
monounsaturated fatty acids present in avocado, nuts, olive,
peanut oils and vegetable oils, and polyunsaturated fatty
acids present mainly in vegetable oils such as sunflower,
sesame, soybean, and corn oils, the prototypical
“Mediterranean” diet) is associated with improving and
promoting the growth of beneficial gut microbial taxa (139,
141).
Although the exact underlying mechanisms through which
diet impacts mental health have yet to be defined, there are
several pathways by which diet can play a role. These
pathways are related to oxidative stress, inflammation, and
mitochondrial dysfunction, which tend to be disrupted in
people with mental health disorders (142). A healthy diet

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typically includes various bioactive compounds that

beneficially engage these pathways. For example, fruits and
vegetables contain fiber, vitamins, minerals, and are packed
with a large number of polyphenols. These nutritional
factors appear to be associated with decreased depression
rates, possibly due to their anti-inflammatory,
neuroprotective, and prebiotic properties (143, 144). On the
other hand, unhealthy diets are rich in nutritional factors
that may negatively engage these pathways. Specifically,
elements commonly found in processed foods like artificial
sweeteners, emulsifiers, and saturated fatty acids may
change the gut microbiome's composition and activate
inflammatory pathways (136).

Probiotics and Depression

In addition to diet, we propose that probiotics are an
essential part of an encompassing approach to treating
depression. We assert that probiotics will help to serve the
critical function of rebalancing the microbiome. While we
recognize that the study of probiotics in humans is a newly
emerging field that has recently gained an immense amount
of attention, published evidence suggests that probiotics
will play a promising role in combating depression (145).
Numerous studies conducted on both humans and animals
have indicated that probiotics are associated with a
reduction in anxiety and depression (78, 80, 146–149).
Other clinical studies have shown that probiotics have also
effectively mitigated anxiety and depressive symptoms in a
manner that is comparable to that of conventional

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prescription medications (150–152). Additionally, related

studies have indicated that probiotic use reduced depressive
symptoms and improved the functionality of both the HPA
axis and was equivalent to treatment with the antidepressant
Citalopram in murine studies (106, 146, 152). However, as
with any emerging therapeutic option, some failed to
achieve the desired effect, a result that has been reported in
a number of studies (153–155).
One particular study gave patients suffering from chronic
stress a 3-week probiotic regimen that contained
Lactobacillus casei. Subjects in the bottom third of the
elated/depressed scale demonstrated the most improvement
as they consistently rated an overall happier mood (150).
Additionally, a double-blind, placebo-controlled
randomized study examined the effects of probiotics on
behavior, brain function, and gut microbial composition in
45 healthy volunteers. At the end of the 4-week period,
probiotic administration was associated with shifts in gut
microbiome profiles and brain activation patterns. The
probiotic arm in this study contained the following nine
bacterial strains: Lactobacillus casei W56, Lactobacillus
acidophilus W22, Lactobacillus paracasei W20,
Bifidobacterium lactis W51, Lactobacillus salivarius W24,
Lactococcus lactis W19, Bifidobacterium lactis W52,
Lactobacillus plantarum W62 and Bifidobacterium bifidum
W23 (156). Using probiotics that incorporate multiple
strains may provide better benefits than those using single
strains and may result in having synergistic effects that can
substantially enhance the establishment and
competitiveness of a putative probiotic strain in the GI tract.

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In this regard, a review by Sun and Buys showed that

consumption of probiotics that have multiple strains in
combination as well as of probiotics containing
Lactobacillus acidophilus, a mixture of Lactobacillus
acidophilus and Bifidobacterium lactis, or Lactobacillus
plantarum led to a statistically significant reductions in total
and low-density lipoprotein (LDL) cholesterol levels, while
clinical trials that used a single strain did not (157). We
speculate that each strain may contribute differently (e.g.,
some produce more beneficial short chain fatty acids
(SCFA), while others antagonize pathogenic
microorganisms present in the gut).
In addition to the strains previously mentioned,
Bifidobacterium infantis (146), Lactobacillus helveticus
(106, 147), Lactobacillus rhamnosus (78), and
Bifidobacterium longum (137) have also been associated
with a reduction in depression. Studies have suggested that
probiotics with such bacterial strains modify the
microbiome and potentially treat depression due to their
ability to normalize cortisol levels, regulate the HPA axis,
and reduce circulating pro-inflammatory cytokines (96,
106).
Potential disruption of gut microbiome caused by
COVID-19 result in colonization of the gut with
opportunistic pathogens, increasing the risk of biofilm
formation that was shown to be associated with many GI
diseases (158, 159) that are resistant to standard treatment.
In a recent study a probiotic combination of Saccharomyces
boulardii, Lactobacillus acidophilus, Bifidobacterium
breve, and L. rhamnosus was shown to provide anti-biofilm

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activity in vitro against polymicrobial biofilms formed by

C. albicans or C. tropicalis when combined with
Escherichia coli and Serratia marcescens (160). Thus, use
of probiotics may help in restoring gut microbiome balance,
as well as, reducing the risk of biofilm formation.
The underlying mechanism/s for the contribution of
probiotics to rebalance the microbiome, normalize
neuroendocrine system, and reduce depression may be
mediated by: (1) immunomodulatory effects of the
probiotics, (2) ability to decrease intestinal translocation of
microbial constituents across the gut intestinal barrier, and
(3) inhibition of digestive biofilms. However, the studies
that suggest these potential influences are mainly
associative, with little mechanistic considerations. The
potential involvement of immunomodulatory effects of
probiotics (e.g., B. pseudocatenulatum) is indicated by a
pronounced decrease of stress-induced interleukin (IL)-18
levels in the serum as well as decrease of basal and stress-
induced interferon gamma (IFNγ) levels in the small
intestine of probiotic-treated animals. Additionally,
probiotic incorporation led to a reduction of corticosterone
in stool and catecholamines in the hypothalamus, as well as
anxiety-like behavior (161). Such findings indicate that
probiotic therapies may produce certain benefits over
current therapeutic drugs or play an adjunctive role. As a
result of this, we propose that probiotics may play an
important part of a comprehensive approach to rebalancing
the microbiome and treating depression.

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Lifestyle Habits and Depression

The last element proposed for combating depression
focuses on 3 specific lifestyle habits; exercise, sleep, and
stress management. The gut microbiota is an extremely
dynamic system that constantly changes over time due to a
combination of various factors and lifestyle habits. Since
the beginning of COVID-19 pandemic, the fear of being
infected, loss of loved ones, lockdown, and social isolation
all together caused marked changes in individuals'
behaviors in an attempt to combat the stress caused by these
factors. This in turn caused a huge impact on daily activities
in multiple aspects including physical activity (162), eating
habits (128), and sleeping (163). We propose that these
three lifestyle habits are critical as a result of the existing
evidence that demonstrates their unique benefits in
improving gut health and decreasing depression.
Exercise and Depression
The first lifestyle habit addressed is exercise. Studies
showed that COVID-19 negatively affected daily physical
activity, thereby shifting individuals to more sedentary
lifestyle (164). Zheng et al., investigated the impact of the
pandemic on physical activity in a sample of 631 young
adults. In total, 70% of the participants reported decreased
physical activity levels since the onset of the COVID-19
pandemic with a significant increase in sleep duration and
sedentary behavior (e.g., computer/video games, sitting
talking on telephone, doing computer/paper work),
consistent with data reported by Moore et al., demonstrating
significant decline in all types of physical activity among

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children and adolescents in Canada since the beginning of

the pandemic (164). A recent review has shown that regular
exercise plays an important role in increasing the diversity
of the gut microbiota and maintaining the balance between
beneficial and pathogenic bacterial communities (165).
Consequently, this major decline in physical activity
eventually causes significant disruption to the gut
microbiota (i.e., dysbiosis) which in turn plays a role in
multiple neuropsychiatric disorders (e.g., depression), as
reviewed by Belizario and Faintuch (166).
We propose exercise as a significant lifestyle habit to
consider due to its relationship with the microbiome and
depression. Exercising is associated with various benefits
that can be directly or indirectly related to microbiome
health. For example, studies have indicated that many
conditions involving inflammation, like depression, can be
treated through exercise (167). Additionally, in clinical
studies, exercise has been shown to reduce depressive
symptoms (168–171) and the effects of stress-induced
intestinal barrier dysfunction has been demonstrated using
murine models (172).
The underlying mechanism/s responsible for the reduction
in depression symptoms associated with exercise is unclear.
However, a number of mechanisms have been proposed
including the thermogenic, endorphin, and the monoamine
hypothesis. Animal studies provide supportive evidence to
the latter hypothesis where an increase in the availability of
the brain neurotransmitters dopamine (a feel-good
endorphin), norepinephrine, and serotonin have been
observed in plasma, urine and various brain regions

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following exercise (168). Recent rodent studies continue to

suggest that exercise may alleviate depression through
common neuro-molecular mechanisms (173, 174),
including increased expression of neurotrophic factors [i.e.,
Brain-derived neurotropic factor (BDNF)], regulation of
HPA-axis activity (175), increased availability of serotonin
and norepinephrine (176), and reduced systemic
inflammatory signaling (177). These activities stimulate the
development of new neurons, increase cerebral vasculature
in human as well as animal studies (178, 179) and synaptic
connections between neurons thereby boosting cognitive
function with the ultimate result of reducing depression
symptoms.
While the exact reasons are unknown, the evidence is
abundantly clear that exercise helps to decrease depression
and depressive symptoms. As a result of these findings, we
propose that exercise is a critical lifestyle element to
consider when dealing with depression. Specifically,
performing a minimum of 150 min of moderate exercise
every week, consistent with the U.S. government's Physical
Activity Guidelines for Americans (180) and the American
Heart Association's recommendations, may improve
depressive symptoms (181).
Sleep and Depression
In addition to exercise, sleep is another essential lifestyle
element to consider, as it is also associated with the
microbiome and depression. When it comes to sleep and the
microbiome, sleep has been shown to have a direct impact
on the microbiome in many ways. For example, murine

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studies have demonstrated the link between sleep

deprivation or disruption and microbial dysbiosis (182,
183).
Gualano et al., investigated the effects of Covid-19
lockdown on mental health and sleep disturbances in a
clinical study in Italy and showed an increase in the
prevalence of depression and anxiety symptoms and sleep
disturbances during the Covid-19 lockdown compared to
before the lockdown 24.7 and 23.2% of the participants
reporting depression and anxiety symptoms, respectively;
while 42.2% had sleep disturbances (163). This was in
agreement with other studies that assessed the impact of
COVID-19 lockdown on mental health in Italy and China
(21, 30, 184–186).
Lack of sleep may lead to and exacerbate depression and
depressive symptoms. In fact, numerous studies have shown
that individuals with depression experience trouble falling
or staying asleep (187, 188), and individuals who have
sleeping problems are more likely to become depressed in
the future (189–192). These findings highlight the critical
role sleep plays in depression and its impact on the
microbiome. As a result of this, we propose that obtaining
adequate sleep is a vital lifestyle element to consider when
treating depression. Specifically, adults should attempt to
receive 7–9 h of sleep per night, as suggested by the
National Sleep Foundation's recommendations (193).
The relationship between sleep and the microbiome is bi-
directional where the microbiome can affect our sleep
pattern and sleep can impact the microbiome composition.
Smith et al. (194) investigated the associations between

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sleep and the microbiome in human clinical studies and

showed that microbiome diversity (richness and Shannon
diversity indices) was positively correlated with sleep
efficiency, and total sleep time, while negatively correlated
with sleep fragmentation (characterized by repetitive short
interruption of sleep). These findings suggest that gut
microbiome diversity promotes healthier sleep. Specifically,
richness within the phyla Firmicutes and Bacteroidetes
were positively correlated with sleep efficiency. Other
authors showed that in humans these two phyla are
associated with sleep quality, circadian rhythm (internal
process that regulates the sleep-wake cycle) and food
intake, factors known to influence sleep quality (195, 196).
Unlike Firmicutes and Bacteroidetes phyla, richness within
the Actinobacteria phylum was shown to negatively
correlate with the number of awakenings. In other words,
increased richness within this phylum contributes to high
sleep quality. The positive effect of the identified phyla on
sleep could be attributed to their ability to secret the
metabolite γ-aminobutyric acid, a neurotransmitter known
to promote sleep (197).
The effect of sleep on the gut microbiome has also been
investigated. Studies by Li et al. showed that a shift in
circadian rhythms can elicit a change in the intestinal
microbiota (198). While a publication by Benedict et al.
showed that after 2 days of partial sleep deprivation vs.
after 2 days of normal sleep, subjects had a significant
increase in Firmicutes:Bacteroidetes (F/B) ratio, a measure
thought to influence the maintenance of normal intestinal
homeostasis. An increase or decrease in F/B ratio is often

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regarded as dysbiosis, however newer studies also question

the reproducibility of this ratio (199). Furthermore, 2 days
partial sleep deprivation resulted in an increase in the
abundance of Coriobacteriaceae and Erysipelotrichaceae
families, and reduced levels of Tenericutes (all P < 0.05).
However, partial sleep deprivation did not have any effect
of ß-diversity. These findings suggest that sleep deprivation
in human subjects can induce alterations in bacterial
families residing in the gut (200).
Interestingly, Li et al. (198) suggested that a bidirectional
connection between the gut microbiome, sleep and
depression exists with inflammation and endocrine
hormones contributing to this process. In this regard, sleep
loss, prolonged disturbances of circadian rhythms, and
depression affects the metabolism of commensal gut
bacteria and leads to alterations in microbiome structure
including a reduction in members of the Lactobacillaceae
family and an increase in Enterococci, Bacteroides
multiforme, Lachnospiraceae, and Ruminococcaceae. These
changes lead to microbiome dysbiosis (201–203). Damage
to the gut epithelial barrier, as happens in leaky gut, will
allow bacterial cells and their harmful metabolites to
stimulate inflammatory immune responses thereby exciting
the vagus and spinal afferent nerves (204). It has been
postulated that the underlying mechanism for this process
may be that the inflammatory response brought about by
gut microbiome dysbiosis exacerbates insomnia and
depression (112, 205–208).
Stress and Depression

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The last major lifestyle habit that comprises a complete

approach to combating depression is effective stress
management. We propose that stress management is an
important lifestyle habit mainly because stress heavily
impacts the microbiome and is related to depression. As a
result of the gut-brain axis, there is always a link to the gut
when a stress response occurs (97). For this reason, stress
has been shown to have a significantly negative impact on
the microbiome as it affects intestinal barrier function (209)
and host-microbe interactions (210). Studies have
demonstrated that various types of stressors, including the
burden of COVID-19 pandemic (211–213), heat, social
rejection, and separation, are responsible for compositional
alterations to the gut microbiome (207, 214–218). In this
regard, a murine study by Galley et al., showed that colonic
lumen tissues were differentially affected by exposure to the
psychological stressor imposition of restraint. Specifically,
restraint stress significantly reduced the alpha diversity in
the microbiome of stressed mice compared to controls.
Moreover, a significant reduction in the relative abundance
of the genera Lactobacillus and Adlercreutzia was observed
(219).
In response to stress, the HPA axis produces cortisol to help
the body deal with danger (220). This type of stress
response relates to an array of neurological issues, including
depression. In fact, studies have shown that the
hyperactivity of the HPA axis is one of the most common
neurobiological changes in patients suffering from
depression (221, 222). Additional research has also
demonstrated a “robust and causal” relationship between

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stressful life events and depression (223). Furthermore, a

gastrointestinal connection exists as stress is a top risk
factor for IBS, which is often linked to depression as
outlined in recent review articles (224–226).
As such, we propose that effective stress management is an
essential lifestyle habit to explore when combating
depression. Specifically, the following stress management
strategies, which include, but are not limited to, the
following: taking time for hobbies, fostering healthy
friendships, volunteering, seeking counseling when needed,
and other relaxation techniques like yoga, meditation, deep
breathing, and massage treatment.
While we understand that various lifestyle habits can
positively impact depression, treatment should also include
psychological, neuropsychiatric and pharmacological
approaches. We propose that exercise, sleep, and stress
management are among the most accessible methods to
individuals that can be relatively easily implemented. Given
the various research studies that have linked the
microbiome and depression with these three particular
lifestyle habits, we propose that this approach may hold
promise.
Proposed Approach to Rebalance
the Microbiome and Reduce
Depression
Having highlighted a relationship between depression and
the microbiome, and the given association of COVID19
with stress and depression, we propose that one approach to

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combat depression should include potential diet

modification, nutritional supplements and lifestyle changes.
Specifically, increasing the abundance of beneficial
organisms that exhibit a reduction in their levels during
stress and depression (e.g., F. prausnitzii, Bifidobacterium,
and Lactobacillus) and decrease the levels of pathogens
such as Candida, Corynebacterium and Ruthenibacterium
should provide an improved gut microbiome.
A Prototypic Diet
Healthy eating habits involving limiting consumption of
sugar and refined carbohydrates and are associated with a
decreased risk of depression. One such diet, the Total Gut
Balance (TGB) (97) incorporates all aspects of the
microbiome using foods and lifestyle practices to support a
healthy gut and reduce overall inflammation with potent
anti-inflammatory and antioxidant foods rich in targeted
vitamins, minerals, and other beneficial constituents. This
diet is nutritionally balanced, whole-food based, low-
glycemic rich in fiber and resistant starches, low in sugar,
full of mono- and polyunsaturated plant fats, low in
saturated fat and animal fat, incorporating lean plant protein
and animal protein primarily from seafood, with some
poultry, as outlined in Table 1. As shown, this diet closely
resembles the “Mediterranean” diet in the makeup of the
constituents (227).

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"
Table 1
Overview of the total gut balance diet.
Adherence to the TGB diet was evaluated in a small clinical
study of 10 individuals (228) where it was noted that the
TGB diet counteracts microbiome imbalance.
Overabundance of Proteobacteria in the GI tract reflects
microbiome imbalance and an unstable gut microbiome
structure that could lead to inflammatory symptoms.
Moreover, previous animal studies suggest that the
microbial dysbiosis in IBD is associated with an increase in
the levels of pathogenic Proteobacterial taxa such as
Enterobacteriaceae (e.g., E. coli) and a reduction in
protective Firmicutes species such as F. prausnitzii (229).
Individuals participating in the TGB exhibited an increase
in F. prausnitzii, an organism reduced in depressed subjects.
In contrast, high levels of F. prausnitzii are found in healthy
subjects (230). F. prausnitzii is a butyrate producer that has
shown anti-inflammatory effects using in vitro and in vivo
mouse colitis models. Finally, a decrease in the abundance
of pathogenic Candida spp. was also observed in TGB
participants.
The observed increase in the level of Roseburia, a Gram-
positive anaerobic bacterium, may have a positive impact

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on the microbiome of depressed individuals. Roseburia is a

commensal bacterium that produces short chain fatty acids
(SCFA), especially butyrate, which are anti-inflammatory
and shown to help maintain immunity (231).
In addition to the described shift in the bacterial and fungal
gut communities of TGB participants, an increase in
abundance of beneficial fungi and bacteria and a
corresponding decrease in harmful microorganisms, a shift
associated with reported improved GI symptoms, less
fatigue, more energy, better sleep, and fewer cravings for
empty-calorie foods was also reported (228).
Studies have shown that bacteria inhabiting our gut have the
ability to produce and/or consume a wide range of
mammalian neurotransmitters, including dopamine,
norepinephrine, serotonin, or gamma-aminobutyric acid
(GABA) (91–95, 232). Since it is well-known that
disturbance of these neurotransmitters is linked to a variety
of mental disorders including depression (233–237), a target
of many antidepressant pharmacological treatments, a
possible approach to rebalance these neurotransmitters,
although not completely discovered, is by modulating the
abundance of these bacteria. However, some gut-derived
neuro transmitters function differently from brain-derived
neurotransmitters (238). It has been reported that
Bifidobacterium improved the expression of Tph1 and
secretion of 5-hydroxytryptophan (5-HTP) in RIN14B cells,
significantly reduced depressive behaviors of mice, and
increased the level of 5-hydroxytryptamine and brain-
derived neurotrophic factor concentration in brain (239).
Furthermore, in some studies, autistic patients were found

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to have increased level of Clostridia that were associated

with production of toxic compounds, such as 3-
hydroxypropionic acid (240) and p-cresol (241), found to
inhibit the dopamine beta-hydroxylase that converts
dopamine to norepinephrine in neurons in the brain and in
the sympathetic nervous system (242). This increase in
dopamine in neurons leads to production of oxidative
species, depletion of glutathione and subsequently brain
damage (240, 243, 244). Thus, increasing these beneficial
organisms while decreasing pathogenic ones through diet
may help in rebalancing neurotransmitter and reducing
symptoms of some mental disorders including depression.
However, investigations in this regard is still ongoing and
thus can't be used as a solo treatment option.

Probiotics
Based on association between COVID-19 infection and gut
microbiome disruption, a logical approach to help balance
the gut microbiome is administration of probiotics.
Probiotic, as defined by World Health Organization, is “live
microorganisms which when administered in adequate
amounts confer a health benefit on the host” (245, 246). Not
only should probiotic consumption restore the gut balance,
it may also decrease the likelihood of colonization of the
gut by opportunistic pathogens (247), as reported in many
studies that analyzed the gut microbiome in COVID-19

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infected patients (57, 58). Published reports have shown

that use of a probiotic helped in supporting the immune
system (248), as well as leading to a marked reduction in
the incidence of respiratory tract infection (249)
Furthermore, studies have also shown that lactic acid
bacteria probiotics possess antiviral properties (250) which
has been used in many fields including agriculture (251),
poultry (252), and medicine (253).
Lifestyle Recommendations
Eating to enhance the microbiome may help to achieve
better health, but there is compelling research to show that
other aspects of life, from the environment you live in, as
well as sleep, stress, and exercise, that can significantly
impact all gut microbes. While genetics is certainly part of
this equation, and diet is another component, research
continues to demonstrate that lifestyle factors play an
important role in chronic diseases (254, 255). Because
depression has been shown to be linked to dysbiosis in the
microbiome, knowing what you can do to make your
lifestyle habits work for you instead of against you is also
important. To aid this approach, we propose a number of
lifestyle recommendations that may enhance the
microbiome balance which should result in reduced
depression. A summation of the recommended lifestyle
targets is listed in Table 2.

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"
Table 2
Lifestyle recommendations.
Conclusion
As a result of the toll COVID-19 has had on mental health,
and society's imperfect understanding and inability to
adequately treat depression, we propose it is important to
examine more thoroughly new potential methods to prevent
and treat depression. While this topic still needs further
examination, research is extremely promising and should
offer a glimpse of hope. The overall goal of the present
manuscript is to offer suggestions that incorporate an
encompassing approach to combat depression. As such, we
want to emphasize the importance of rebalancing the gut
through probiotics, diet, and lifestyle changes. However, we
also propose that more can and should be done to achieve
this goal and improve the lives of individuals who are
struggling.
Regardless of whether people have seen a decrease in their
own mental well-being since the start of COVID-19,
everyone needs to be responsive and work together to
effectively bring an end to this mental health crisis. We
propose that the first step toward progress is awareness.
However, each of us cope with increased stressors in our
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own unique ways, such as remaining busy, spending time

with family and friends, etc. It is critical to note that some
community members are overwhelmed and are desperately
in need of assistance. For these reasons, we recommend
checking in on your loved ones and asking how you might
be able to assist them during these unprecedented times.
Since the start of time, humans have continued to evolve
and adapt to whatever situations they are presented with.
We propose that the COVID-19 pandemic is no different
from these situations. Therefore, if you find yourself
constantly worrying about the future, we hope this paper
has eased your concerns and allowed you to adopt our
optimistic view that we will get through this and be better
because of it.

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