ASSOCIATE PROFESSOR, DEPARTMENT OF PHARMACOLOGY, NIET, PHARMACY INSTITUTE, GREATER NOIDA.

1. Challenges to come up with Functional Gastro
Intestinal Disorder (FGID) during COVID-19 pandemic
Dr. Saumya Das
Associate Professor, Pharmacology,
NIET, GREATER NOIDA

2. Introduction
• The emotive digestive system is the connection
between the brain and gut. The feeling of
indigestion and heartburn also stems from the same.
Nowadays, when stress because of the COVID-19
pandemic is on rise, a lot of people are also suffering
from gastric problems.
• Stress and anxiety trigger contractions in the
gastrointestinal tract which cause these stress-
related digestive problems.
• "Functional" is a term generally given to the
disorders when normal body functions like
movement of the intestines, nerves sensitivity of the
intestines, or normal functioning of the brain parts
which control these functions are impaired.
Contd…….

3. Introduction
• Functional gastrointestinal disorders
(FGIDs) manifest as characteristic
combinations of troublesome symptoms
arising from the gastrointestinal (GI) tract.
• They are usually classified according to the Rome criteria (latest one is
Rome-IV), which are based on patients’ self-reported symptoms.
• The clinical severity of FGIDs is estimated to be mild in 40%,
moderate in 35%, severe/complicated in 20%, and very severe in 5% of
affected patients.

4. Characteristic of the FGIDs
• Functional gastrointestinal disorders (FGIDs)
are a group of gastrointestinal (GI) disorders
that include various combinations of chronic or
recurrent GI symptoms not explained by
structural or biochemical abnormalities.
• Functional dyspepsia (FD) and irritable bowel
syndrome (IBS) are among the most widely
recognized FGIDs.
• Each entity has no specific objective findings,
and that they overlap with each other. Therefore,
these entities are syndromes, and their diagnosis
and treatment are similar. Diagnosis of FGIDs is
based on patients’ self-reported symptoms.
Therefore, the definition of the symptoms may
differ by countries and geographic areas.

5. A recent study was conducted on 73,076 persons where women participants
were 49.5% . Data were collected via the Internet in 24 countries, personal
interviews in 7 countries, and both in 2 countries, using the Rome IV
diagnostic questionnaire.
The study report was published in April, 2020 in a renowned journal –
‘Gastroenterology’ that 40.3% persons who completed the Internet surveys
and 20.7% of persons who completed the household surveys reported FGID
symptoms. FGIDs were more prevalent among women than men.
World wide Prevalence
Contd……

6. Contd……

8. Classification of FGID
• Several attempts have been made to classify patients in terms of
observed aberrant GI motility. The current diagnostic nomenclature
system (Rome IV) is exclusively based on patient’s symptoms and is
considered to be so far the most appropriate one.
• The Rome I definition was published in 1989, followed by the Rome II
criteria for FGID in 1999.
• The Rome III Criteria were published in 2006.
• The latest Rome IV Criteria were published in 2016. The Rome
classification excludes patients with predominant symptoms of gastro
esophageal reflux disease (GERD) and FGID.

9. Rome I criteria for Irritable Bowel Syndrome (IBS) and
Functional Dyspepsia (FD)
• In IBS minimum three months continuous or recurrent symptoms
of abdominal pain or discomfort which is relieved with defecation
and/or associated with a change of frequency of stool and/or
associated with a change of consistancy of stool are the symptoms
of IBS.
• Two or more of the following symptoms- Altered stool frequency/
Altered stool form (hard or loose/ Lumpy/ watery)/ Altered stool
passage (urgency or feeling of incomplete evacuation, straining)/
Bloating or feeling of abdominal distension/ Passage of mucus
atleast at 25% will confirm IBS.
• In FD there is chronic or recurrent abdominal pain for three months
or more or discomfort of the upper abdomen or no clinical,
endoscopic or ultrasonographic evidence of any known organic
disease that is likely to explain the symptoms, biochemical and no
history of major gastric or intestinal surgery.

10. Rome II criteria for FD and IBS
• In FD, at least 12 weeks, need not to be consecutive, in the preceding
12 months of recurrent or persistent discomfort or pain centered in the
upper abdomen with no evidence of organic disease.
• There is also no evidence that dyspepsia is exclusively relieved by
defecation. In addition a sub classification also has been made on
predominant symptom - dismotility like dyspepsia, ulcer like
dyspepsia and unspecified dyspepsia.
• In IBS at least 12 weeks, which need not be consecutive, in the
preceding 12 months of pain or abdominal discomfort that has 2 of 3
features like relief with defecation, onset associated with the change in
form (appearance) and frequency of stool (Drossman et al., 2000).

11. Comparison of Rome-III and Rome- IV criteria

13. Functional Dyspepsia

14. Pathophysiology of FGID
Gut-Brain Axis
“Gut” is the group of organs which starts from
mouth, esophagus, stomach, small intestine,
and ends with colon. This helps in the
transformation of food into the smaller
nutrients inside body. The “gut reactions” may
be disruptive and painful. Thus gut-brain axis
is an important but least recognized
parameters in human health. If a person
experience gut symptoms though he/she is
under perfect health diet, then it may be
because of gut-brain axis issues. There are
some defined and also some undefined
relationship between digestive system with
memory, depression, anxiety, cognitive
function and other behavioral and mental
issues. Contd…….

15. • The key players of gut-brain axis are the hypothalamus, frontal cortex, the
insular cortex and the vagal motor nuclei. The brain basically communicates
with the gut via neuronal projections and then hormones that are secreted via
the hypothalamus.
• The frontal cortex primarily stimulates the vagal nuclei to initiate gut motility
(intestinal peristalsis), by which food contents move through the digestive tract,
and do enzymes secretion.
• The somatotopic map present in the insular cortex, provide information
regarding the location of gut.
• The vagal motor nuclei stimulate intestinal motility, further modulate blood
flow. These in turn activate the release of hydrochloric acid and digestive
enzymes.
Contd…….

16. • The enteric nervous system has a major role in the gut, the intestine’s immune
system, gut-associated lymphoid tissue, and also the intestinal microglia.
• Firstly, the intestinal motility and enzyme release is performed by enteric
nervous system and then the incoming input conveyed is to the vagus nerve.
• Enterochromaffin cells in gut contain almost 80% of the total body’s
serotonin and this acts primarily to regulate peristalsis and motility.
• This is the pharmacological correlation of depression and constipation often
appear together.
• Remaining 20% of serotonin is produced in serotonergic neurons in the CNS
which regulate appetite, mood, muscle contraction and sleep.
• So the cytokines, gut opiates, gut peptides like neurotensin and substance-P
communicates gut with the brain.
Contd…….

17. • FGIDs show symptoms which are derived from different combinations of physiological
activities: enhanced motor reactivity, increased visceral hypersensitivity, change in
inflammatory function and mucosal immune (including changes in bacterial flora), and
altered CNS-enteric nervous system (ENS) up or down regulation (influenced by
sociological and psychosocial factors and exposures).
• Irritable Bowel Syndrome (IBS) is a complex phenomenon, and results in various
disorders like dysmotility, mucosal immune dysregulation, visceral hypersensitivity,
alterations of bacterial flora and CNS-ENS dysregulation.
• FGIDs are not psychiatric abnormalities, though psychological difficulties and stress can
worsen FGID symptoms.
• IBS is the most common FGID, in which bowel consistency is altered in combination
with abdominal pain.
• The other general symptoms are ulcer-like symptoms, Dyspepsia with upper-GI pain,
indigestion problem or milder discomfort with stomach fullness and in many times
nausea immediately after eating.

18. There are three primary characteristics of FGIDs - brain-gut
dysfunction, motility and sensation:
• Motility (e.g., peristalsis) is the smooth muscle activity of the GI tract. Normally
motility is a sequential muscular contractions from the start to the end of GI tract.
In FGIDs, the peristalsis is abnormal - there may be muscular spasms which can
cause pain. The muscular contractions can be very rapid (fast movement is
diarrhea) or very slow (slow movement in constipation).
• The nerves of the GI tract cause sensation to stimuli (digesting a meal). In
FGIDs, sometimes the nerves are so sensitive that normal contractions also can
cause pain or discomfort.
• Brain-gut disorder relates to the altered communication between brain and GI
tract. In FGIDs, the coordination between the gut and brain function may be
impaired and this can lead to bowel difficulties, increased pain which can be
worsened by stress or anxiety.

19. Physiology of FGID
1. Motility
• Propulsion along the human digestive tract helps in digestion and absorption.
• Local inflammatory, immune or degenerative, infilterative and factor scan directly influence the
smooth muscles, of the GIT or the ENS effector system.
• Visceral afferent fibers indirectly can induce dysmotility via prevertebral ganglia and trigger
autonomic changes inside brain stem, such as alteration in heart rate, and colonic tone. Psychosocial
factors can also initiate alterations in GI motility.
• Patient with any of the FGID symptoms have more stress induced GI motor response conditions than
control group.
2. Inflammation and post-infectious IBS
• Gastroduodenal inflammation has also been reported in dyspepsia paients who are devoid of ulcer.
• A meta-analysis has done for an inflammation in the plexus myentericus in IBS patients and
increased cases of IBS after gastroenteritis.
• Post infectious IBS, diagnosed by a little inflammation with increased number of T lymphocytes and
mast cells, is formed with a prevalence rate of 6-7% after an acute attack of bacterial gastroeneteritis.
Anxiety, depression, neurosis, female gender, a severe episode, somatization are risk factors for
initiation of post infectious IBS.
Contd…..

20. 3. Bacterial flora
• Patients with H. pylori infection with non-ulcer dyspepsia, eradication of
H. pylori may be a sucessful therapy.
• Though, followup studies after one year showed eradication of H. pylori,
it actually produced no benefit when compared with placebo or when
compared to antacid therapy.
• The fecal microbiota was also changed in IBS patients and a connection
between antibiotic therapy and IBS has been documented.
• IBS patients may give positive response to the use of probiotic bacterial
compositions and the eradication of GI bacterial growth.

22. Role of neurotransmitters in the management of FGID
• Different findings have showed that serotonin (5-HT) is
an important neurotransmitter in the enteric nervous
system (ENS), as well as in the CNS.
• It plays a major role in the stimulation and inhibition of
pain pathways and also in the initiation of the peristaltic
reflex.
• Serotonin is well distributed throughout the gut
predominantly in the enterochromaffin cells of the
mucosal crypts and, to a lesser extent, in the nerve fibers
of the submucosal and myenteric plexuses.
• 5-HT exerts its wide range of activities through its actions
on various receptor subtypes. In the GIT, 5-HT3 and 5-
HT4 are the primary receptors subtypes.
Contd……

23. • However, 5-HT1A, 5-HT1C, 5-HT1P, and 5-HT2 receptor subtypes have
been identified on enteric nerves or on smooth-muscle cells of GI tract.
• There are equal importance of 5-HT in gut as well as in the CNS. The
role of 5-HT has diverse functions and dysfunctions, including those of
memory and learning, sleep, mood, appetite, sexual behaviors and
homeostasis.
• Altered 5-HT levels are thought to play a role in many CNS disorders,
including obsessive-compulsive disorder (OCD), generalized anxiety,
major depressive disorders, phobias and also in thought disorders such
as schizophrenia.
• Many of these extraintestinal symptoms generally noticed as comorbid
conditions in patients suffering from functional GI disorders.

24. Correlation of Psychological stress with GI symptoms
• According to the evolving theory, the chronic GI
symptoms are initiated by a combination of
intestinal motor, sensory and CNS activity.
• Bi-directional pathways between the central and
enteric nervous systems, (brain-gut) axis
correlate these associations.
• These bi-directional pathways bridge the
sensation in the intestinal motor function and
gut. External stressors and cognitive information
(thought and emotion) have neural connections
to the brain, which in turn affect GI sensation,
GI secretion and motility.
• The findings showed that not only the brain
affects the gut, but gut activities also affect
central pain perception, mood and behavior.

25. Impact of Functional Disorders in quality of life (QOL)
• The feelings like emotion, anger, anxiety, sadness can trigger
symptoms in the gut. The brain has also direct effect on the gut. For
example, even the thought of eating can release the stomach’s digestive
juices before food gets there.
• This connection present in both ways. An altered intestine can send
signals to the brain and vice versa.
• Therefore, a person’s stomach or intestinal distress can either be the
cause or the product of anxiety, stress, or depression. Thus the brain
and the GIT are intimately connected.

26. • Functional abdominal pain disorders (FAPDs) affect 10–25% of school-aged
children.
• The biopsychosocial model explains FAPDs as the result of the interplay of
multiple factors including visceral hypersensitivity, gut dysbiosis, motility
abnormalities, abnormal gastrointestinal reactivity to physiological (e.g.,
dietary) or noxious stimuli (toxin) or psychological stress.
• Children with FAPDs have higher rates of school absenteeism, sleep
problems, comorbid somatic pains, depression, and anxiety all resulting in an
overall decreased quality of life (QOL).
• FAPDs are classified per the Rome IV criteria into four diagnoses: irritable
bowel syndrome (IBS), functional abdominal pain (FAP), functional
dyspepsia (FD), and abdominal migraine.
• There has been an increased interest by parents towards the use of alternative
treatments that are perceived as “safe and natural”.
• Dietary management is one of the most commonly used CAM interventions.
FAPD

27. Treatment of FGID
General dietary and lifestyle alterations include

28. Lifestyle And Dietary Modifications To Improve Gut-Brain Function
One of the best known ways to improve mental health is through gut. Like the brain, the gut also
has its own nervous system and informations from the gut goes to the brain via the vagus nerve.
Exercise and acupuncture are the two of the best ways to
enhance blood flow to brain. Some research suggests that
vinpocetine from periwinkle can enhance blood flow to the
Brain. There are also certain botanicals and nutrients like
ginko, feverfew (Tanacetum parthenium L.)
which increases the blood supply to brain. Yoga and other stress reduction methods also help to
manage the stress level.
Food which enhances the gut healing include probiotics, jerusalem artichokes, prebiotic foods
like sweet potatoes.

29. a. Fatty Fish
It has seen in studies that diet which are deficient in omega-
3 fatty acids, such as docosahexaenoic acid (DHA) and
eicosapentanoic acid (EPA), and high in trans fats and saturated
fats, negatively affect the brain. Since brains are made up
largely of fatty tissues and body cannot synthesize essential
fatty acids, subjects have to depend on omega-3 fatty acid rich
diet to meet daily needs.
Researchers have found that foods high in omega-3 fatty acids,
reduce symptoms of schizophrenia, attention deficit,
hyperactivity disorder, depression and other mental disorders.
Omega-3 fatty acids have crucial role on the production of
neurotransmitters, including dopamine and serotonin. By
supporting the synapses in the brain, omega-3 fatty acids also
boost learning and memory.

30. b. Whole Grains
Glucose provides the primary source of energy for the brain, which
comes from carbohydrates. Simple carbohydrates exacerbate low
mood by creating spikes in blood sugar and have been shown to have
effects on the brain. On the other hand complex carbohydrate
releases glucose slowly, supply nutrition to the brain and body for
long time. Natural sources of complex carbohydrates include whole-
wheat products, barley, beans, soy, oats and wild rice (National
Institutes of Health).
c. Lean Protein
Foods are broken down into substances that are used to make
neurotransmitters and other substances which help in building the
communication system of the body. The amino acid tryptophan, a
building block of protein also alters the mood by producing the
neurotransmitter serotonin.
It is well proved that serotonin is associated with anxiety and
depression. Lean protein sources; including eggs, beans, fish, and
chicken help keep serotonin levels maintained. Though complex
carbohydrates are more important to facilitate the entry of tryptophan
into the brain, thus reducing the symptoms of depression and anxiety
and improving overall cognitive functioning.

31. d. Green leafy vegetables
Leafy greens such as mustard greens, broccoli, spinach, turnip
beets and lentils are high in folic acid.
Deficiencies in folate as well as other vitamin B complex have
been directly linked with higher rates of depression, anxiety,
fatigue and insomnia.
Broccoli contains selenium, a trace mineral that has an
important role in maintaining our immunity, reproduction and
thyroid hormone metabolism.
Some researchers found that low levels of selenium initiate
depression, anxiety and fatigue. Other major sources of
selenium include walnuts, whole-grain products, onions,
chicken, seafood.

32. e. Yogurt
Fermented foods like yogurt with active cultures and certain
pickled vegetables, contain probiotics (healthy bacteria)
which plays an important role to reduce anxiety
and stress disorders and also affect the neurotransmitter
GABA.

33. f. Processed food
Modern diet pattern has significantly changed over
the years. Busy lifestyles, food manufacturing and the
availability of processed foods play an important role
in diet. Intake of fresh fruits and vegetables, avoiding processed foods can improve the
health condition to a great extent.
Literature review reported that the probiotic, known as Bifidobacterium longum NCC3001
normalized the anxiety-like behavior in mice with infectious colitis
Separate research also found the probiotic Lactobacillus rhamnosus had a significant effect
on GABA level regulation in certain brain regions and lowered the stress-induced hormone
corticosterone, which reduced depression and anxiety. The neurons present in brain and also
in the gut releases neurotransmitters like serotonin, which plays an important role in the
management of functional disorders (FGIDs).

34. • Those with mental illnesses also burn out as they try to cope with
multiple responsibilities such as working from home, managing
domestic chores, the threat of a job loss, etc.
• Experts warn that the relationship between the COVID-19 and
mental health problems are “bi-directional”, i.e. such illnesses are
not merely consequences of the pandemic but an inability to deal
with them can lead to the spread of COVID-19 infection.
• Level of depression is four times higher among men as they feel
greater pressure and shame due to financial problems. The majority
of suicides were found to be among those who already suffered
from depression.
COVID and FGID
Contd……

35. • Fear, worry, and stress are normal responses to perceived or real
threats, and at times when we are faced with uncertainty or the
unknown. So it is normal and understandable that people are
experiencing fear in the context of the COVID-19 pandemic.
• Added to the fear of contracting the virus in a pandemic such as
COVID-19 are the significant changes to our daily lives as our
movements are restricted in support of efforts to contain and slow
down the spread of the virus.
• Faced with new realities of working from home, temporary
unemployment, home-schooling of children, and lack of physical
contact with other family members, friends and colleagues, it is
important that we look after our mental, as well as our physical,
health.
Contd……

36. • The immune system may be compromised with the use of
corticosteroids in the management of IBD, make prone the
individuals for viral infections.
• Stress-related digestive troubles may be on the rise as people around the globe
worry in the midst of a Pandemic Stress and Anxiety can trigger more frequent
or stronger contractions in the GI tract which some may perceive as
uncomfortable or even painful.
• In addition to belly pain, stress can trigger a wide range of other gut symptoms
including heartburn, nausea, bloating, a change in bowel pattern, or in rare
cases, even rectal pain. Patients who already have irritable bowel syndrome, a
chronic condition marked by stomach pain, cramping and a change in bowel
habits, may see an uptick in their symptoms.
• Preventive measures in terms of healthy food, avoid unnecessary stress, take
sound sleep and doing exercise can reduce the risk of FGID as well as COVID-
19 infection.

37. THANK YOU