CHAPTER ONE

Introduction

Role of probiotics in gut health

Probiotics, live microorganisms comprising primarily bacteria and yeast, bestow health benefits upon

their host, typically humans, when ingested in sufficient quantities (Sanap et al., 2019). Found naturally in

certain foods and also available as dietary supplements, these advantageous bacteria play a crucial role in

maintaining the microbial equilibrium of the gut (Yang et al., 2020). The well-being of the gut is

intricately intertwined with overall health. A harmonized gut microbiome not only facilitates digestion

but also enhances immune function, nutrient absorption, and even influences mental well-being (Merlo et

al., 2024).

Probiotics function by introducing beneficial bacteria into the gut microbiome. These friendly bacteria aid

in restoring equilibrium in instances where the microbiome has been disrupted, such as following

antibiotic use (Dahiya and Nigam, 2023). They also enhance the gut's capacity to digest food, synthesize

vitamins, and fortify its defense against harmful pathogens (Yang et al., 2020).

Probiotics can offer benefits for various gut-related conditions, including irritable bowel syndrome (IBS),

diarrhea, and inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis (Selvamani et

al., 2022). Certain probiotic strains have even shown promise in alleviating symptoms of lactose

intolerance and promoting regular bowel movements (Sanders et al., 2019).

Beyond gastrointestinal health, probiotics may also exert a favorable influence on immune function and

mental well-being (Casertano et al., 2022). Research indicates that specific probiotic strains can modulate

immune responses, potentially lowering the risk of infections and allergic reactions. Additionally, the

concept of the gut-brain axis underscores the potential role of probiotics in managing conditions such as

anxiety and depression (Gambaro et al., 2020).

Probiotics contribute to the proliferation and differentiation of epithelial cells, along with aiding in the

development and upkeep of the immune system (Maldonado Galdeano et al., 2019). Probiotics are not a

recent innovation but have been present in traditional foods like beverages, salty fishes, yogurt, various

cheeses, and similar items since ancient times (Gao et al, 2021). These food sources harbor diverse strains

of beneficial bacteria. It is conceivable that fermented milk may have been among the earliest instances of

food containing probiotics (Anadón et al., 2021). Early humans recognized the pleasant taste of fermented

milk and subsequently mastered the production of cheese, yogurt, and comparable products (Tamang et

al, 2020). Before the advent of the microscope, humans possessed the knowledge to create various milk

products with distinct flavors and textures (Amara, 2012). This was facilitated by diverse microbial

reactions induced by different microbes (Bourdichon et al., 2012). This accumulated knowledge has been

transmitted globally across generations, facilitating the ongoing production of such foods. The exact

origins of the first use of food containing probiotics, particularly for medicinal purposes, remain

uncertain. Nevertheless, probiotics have collectively been integral to fermented foods, provided the active

microbes are beneficial and capable of colonizing the digestive system (King et al., 2017). Fermentation

using microbes has been practiced since ancient times, with visible fungal growth evident in food even

without microscopes. The public has possessed the knowledge of producing bakery and alcoholic

products since ancient times (Bamforth and Cook, 2019).

Probiotics refer to foods and/or supplements containing non-pathogenic microbes like bacteria and yeast

that colonize the gut and potentially confer various health benefits (Ranjha et al., 2021).

The ability of probiotics to modify the immunological response of the host, antagonize pathogenic

microbes, or compete for adhesion sites with pathogenic microorganisms is related to the action of

probiotics against microorganisms (Khaneghah et al., 2020). Infections of the digestive tract, irritable

bowel, lactose intolerance, allergies, infections of the urogenital tract, cystic fibrosis, and various cancers

can all be prevented and treated with the use of probiotics (Stavropoulou and Bezirtzoglou, 2020). They

can reduce the side effects of various antibodies. In the field of oral health, dental caries, periodontal
disease, and bad breath can be prevented and treated with the use of probiotics (Allaker and Stephen,

2017).

The gut microbiome denotes the intricate community of microorganisms, encompassing bacteria, fungi,

and viruses, inhabiting the digestive tracts of humans (Gomaa, 2020). Within this community, both

beneficial (good) and harmful (bad) bacteria coexist. Beneficial bacteria contribute to digestion,

synthesize vital vitamins, and fortify the immune system (Mohammed, 2024). Conversely, harmful

bacteria can provoke digestive ailments, infections, and other health issues (Zhang et al., 2015). An

imbalance between these two categories, termed dysbiosis, can result in a spectrum of health problems

from gastrointestinal disturbances to chronic diseases (Vijay and Valdes, 2022). Probiotics serve a crucial

role in maintaining this equilibrium. By introducing or replenishing populations of beneficial bacteria,

probiotics assist in suppressing the proliferation of harmful bacteria, thereby fostering a balanced gut

microbiome (Appanna, 2018). This equilibrium ensures optimal gut function, aids nutrient absorption,

and reinforces the body's innate defense mechanisms (Pickard et al., 2017).

The gut microbiome constitutes a sophisticated ecosystem comprising trillions of microorganisms,

encompassing bacteria, viruses, fungi, and various other microbes, inhabiting our gastrointestinal tract.

This microbial community exerts a significant influence on our well-being, undertaking a multitude of

crucial functions (Ahmed and Khan, 2024).

One of the principal roles of the gut microbiome is to facilitate digestion. These microorganisms are

responsible for the breakdown of complex carbohydrates, synthesis of essential vitamins, and assistance

in nutrient absorption from our diet. Furthermore, they play a pivotal part in bolstering the immune

system by forming a barrier against harmful pathogens (Rowland et al., 2018).

Additionally, emerging research indicates that the gut microbiome not only impacts our physical health

but also influences our mental well-being (Karl et al., 2018). There exists a growing body of evidence

establishing connections between the gut-brain axis the bidirectional communication pathway between
the gut and the brain and conditions such as anxiety, depression, and even neurodegenerative diseases

(Bruce and Ritchie, 2018).

The gut is the gastrointestinal system and includes the stomach, intestines, and colon. It digests and

absorbs nutrients from food and excretes waste (Ogobuiro et al., 2023).

Around 200 distinct species of bacteria, viruses, and fungi inhabit your large intestine. These

microorganisms collectively constitute your gut microbiome. The bacteria aid in the digestion process,

transforming food into nutrients that your body can utilize (Richard and Sokol, 2019).

Some bacteria present in the gut might be linked to certain diseases. While certain microorganisms can be

detrimental to well-being, many are advantageous and vital for maintaining a healthy body (Nagpal et al.,

2016).

The well-being of the gut can influence both physical and mental well-being (Karl et al., 2018).

Numerous factors, such as dietary choices, can influence the composition of bacteria in your digestive

system. Dietary habits can exert both short-term and long-term impacts on the environment of the gut

microbiome (Rinninella et al., 2019).

AIMS AND OBJECTIVES

Aim

To investigate and understand the role of probiotics in promoting gut health, focusing on their

mechanisms of action, potential benefits, and impact on overall well-being.

Objectives

i. Evaluate the scientific literature to comprehensively elucidate the mechanisms through which

probiotics contribute to gut health.

ii. Investigate the potential therapeutic effects of probiotics on common gut-related disorders such as

irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), and gastrointestinal

infections.

iii. Examine the influence of probiotics on digestive processes, including their ability to aid in

nutrient absorption, regulate bowel movements, and maintain gut microbial balance.
 CHAPTER TWO

2.1 Literature review

Human beings consume a significant number of pathogens every day, primarily bacteria.

For several decades, probiotic microorganisms have been utilized in several diets due to their

positive effects on human health (Zhang et al., 2015).

The human gastrointestinal tract contains over 1,000 different types of bacteria (Hillman

et al., 2017). Some of these are beneficial bacteria; they can promote health by stimulating the

immune system, improving the digestion and absorption of nutrients, and inhibiting the growth

of pathogens (Wang et al., 2020). Others are more harmful, pathogenic, bacteria which are

responsible for intestinal infections, diarrhoea and constipation, and the production of

carcinogens and toxins (Moammad et al., 2018).

It's believed that probiotics aid in reinstating the innate bacterial equilibrium in your

digestive system, encompassing the stomach and intestines, especially when it has been disturbed

by sickness or medical interventions (Islam, 2020).

Infections of the digestive tract, irritable bowel, lactose intolerance, allergies, infections

of the urogenital tract, cystic fibrosis, and various cancers can all be prevented and treated with

the use of probiotics (Sanap et al., 2019). They can reduce the side effects of various antibodies.

In the field of oral health, dental caries, periodontal disease, and bad breath can be prevented and

treated with the use of probiotics (Bodke et al., 2022). The findings of several of these clinical

studies indicate that probiotics may be beneficial in the treatment and prevention of various

diseases and health issues (Liu et al., 2018). Validation of a significant number of these clinical

investigations is necessary before the results can be applied to the clinical setting. Clinical
studies play an important part in such investigations. In the not-too-distant future, the outcomes

of such trials will determine whether or not probiotics are effective in the treatment of disease

(Bodke et al., 2022).

Probiotics, live bacteria and yeasts advocated for their assorted health advantages, are

typically incorporated into yogurts or consumed as dietary supplements. They are commonly

referred to as "beneficial" or "supportive" bacteria (Kapoor et al., 2020).

Certain indications suggest that probiotics could be beneficial in specific scenarios, such as

alleviating certain symptoms associated with irritable bowel syndrome (IBS) (Kapoor et al.,

2020).

Probiotics, which are live microorganisms, are often advertised as offering health benefits

when ingested, primarily by enhancing or replenishing the gut microbiota (Kumari et al., 2021).

They are generally regarded as safe for consumption, although they may lead to bacterial

interactions with the host and occasional undesirable effects (Durchschein et al., 2016). While

there is limited evidence supporting the usefulness of probiotics for certain conditions, many of

the health benefits attributed to them lack substantial proof (Kumari et al., 2021).

The initial probiotic to be identified was a specific strain of bacillus found in Bulgarian

yogurt, known as Lactobacillus bulgaricus. This breakthrough occurred in 1905, credited to the

Bulgarian physician and microbiologist Stamen Grigorov. The contemporary understanding of

probiotics is often associated with the Russian Nobel laureate Élie Metchnikoff, who proposed

around 1907 that Bulgarian peasants, who regularly consumed yogurt, experienced extended

lifespans (Underhill et al., 2016).

 Probiotics can enhance host well-being by augmenting the population of beneficial

bacteria in the gut (Kumar et al., 2020). These live microorganisms are characterized by their

ability to confer health advantages upon the host when ingested in suitable quantities. They are

present in a range of foods and dietary supplements, encompassing strains like lactobacilli and

bifidobacteria (Kothari et al., 2019). On the other hand, prebiotics, such as inulin and fructo-

oligosaccharides, are indigestible carbohydrates that selectively stimulate the proliferation and

function of beneficial gut bacteria (Guarino et al., 2010).

Probiotics are foods and/or supplements that contain non-pathogenic microbes such as

bacteria and yeast that colonize the gut and can potentially yield a variety of health benefits

(Bodke et al., 2022). Research into the various ways in which probiotic bacteria could be used in

the treatment of intestinal disorders is ongoing. Thanks to clinical studies and laboratory

experiments, we now know more about how probiotics affect gut microbiome disorders. Studies

can prove that probiotics can alleviate a variety of gastrointestinal ailments and improve overall

health (Scott et al., 2015).

Probiotic cultures constitute a component of fermented dairy items, as well as other

fermented edibles and fortified foods (Pimentel et al., 2021).

Lactic acid bacteria (LABs), which are bacteria involved in food fermentation, possess

the capability to forestall food spoilage and enhance the nutritional quality of the foods they

colonize. Acid fermentation, alongside salting, persists as one of the most cost-effective and

energy-efficient means of preserving fresh vegetables, cereal gruels, and milk-cereal mixtures

(Khaneghah et al., 2020).

Fig1: Diagram of immune system (Hillman et al., 2017).
 Fermented products containing lactic acid bacteria encompass an array of items such as

pickled vegetables, kimchi, pao cai, and sauerkraut; sourdough bread or bread-like creations

crafted sans wheat or rye flour; amino acid/peptide meat-flavored condiments and pastes derived

from fermented cereals and legumes; fermented mixtures of cereal-fish-shrimp; and fermented

meats; soy products like tempeh, miso, and soy sauce; dairy goods including yogurt, kefir, and

buttermilk; and non-dairy products like bee pollen (Walsh et al., 2023).

More specifically, sauerkraut harbors bacteria including Leuconostoc mesenteroides,

Lactobacillus plantarum, Pediococcus pentosaceus, Lactobacillus brevis, Leuconostoc citreum,

Leuconostoc argentinum, Lactobacillus paraplantarum, Lactobacillus coryniformis, and

Weissella spp. Kimchi features bacteria such as Leuconostoc spp., Weissella spp., and

Lactobacillus spp. Pao cai encompasses L. pentosus, L. plantarum, Leuconostoc mesenteroides,

L. brevis, L. lactis, and L. fermentum (Walsh et al., 2023). Various other bacteria present in

numerous Asian fermented fruits and vegetables are also documented. Kefir contains strains like

Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus, Lactobacillus

delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Lactobacillus kefiranofaciens,

Lactococcus lactis, and Leuconostoc species (Walsh et al., 2023). Buttermilk carries either

Lactococcus lactis or L. bulgaricus. Other probiotic-accredited acidic bacteria are found in

kombucha, including Gluconacetobacter xylinus, Zygosaccharomyces sp., Acetobacter

pasteurianus, Acetobacter aceti, and Gluconobacter oxydans (Walsh et al., 2023).

 Probiotics play roles in the proliferation and differentiation of epithelial cells, as well as

in the development and maintenance of the immune system (Yousefi et al., 2019). Traditional

foods such as beverages, salty fishes, yogurt, various types of cheeses, and others have long

contained probiotics, predating modern inventions (Katz, 2016). These food items harbor diverse

beneficial bacteria (Yadav et al., 2017). It's speculated that the earliest utilization of probiotic-

containing foods may have been fermented milk (Chen et al., 2024). Over time, humans

discovered the appealing taste of fermented milk and subsequently learned to transform it into

cheese, yogurt, and similar products (Sanders et al., 2018). Even before the advent of the

microscope, people knew how to prepare various milk products with distinct tastes and textures,

thanks to microbial reactions instigated by different microbes (Smykov et al., 2018). This

knowledge has been transmitted across generations globally, perpetuating the production of such

foods to this day. While the precise origins of the first use of probiotic-containing foods,

especially for medicinal purposes, remain unclear, probiotics collectively have been integral to

fermented foods as long as active microbes are beneficial and capable of colonizing the digestive

system. Fermentation with microbes has been practiced since ancient times, observable through

the visible growth of fungi in food. Ancient societies were adept at producing bakery and

alcoholic products, ensuring product quality through the maintenance of seed cultures derived

from successful fermentation processes for subsequent use (Amara, 2012). Although the

contributions of Van Leeuwenhoek and Hooke in 1665 are often highlighted in scientific

discourse, the knowledge and practice of fermentation predate their era (Amara, 2012).

The origins of probiotics may trace back to the earliest humans who consumed milk products or

perhaps even other fermented foods ( Gasbarrini et al., 2016). However, climatic conditions likely

favored the development of traditional sour milk or cultured dairy items (Hati et al., 2019).
Folklore often surrounds the origins of certain probiotics, with some claiming religious roots,

such as the case of Kefir (Santacroce et al., 2019). Amara (2012) recounts the use of probiotics

by the Pharaonic civilization, practices that persist among modern Egyptians, including the

consumption of milk, seeds, fish, and other products.

Ilya Ilyich Metchnikoff, the Nobel Prize winner in Medicine in 1908, working at the Pasteur

Institute, may have been the first to observe the effects of what we now call probiotics ( Anadón et

al., 2021). He associated health and longevity with the ingestion of bacteria found in yogurt

(Anadón et al., 2021). In 1907, he hypothesized that bacteria in yogurt fermentation, specifically

Lactobacillus bulgaricus and Streptococcus thermophilus, suppressed putrefactive fermentations

in the intestinal flora, promoting health (Khan et al., 2020). He linked the long lifespan and good

health of Bulgarian peasants to their consumption of yogurt containing Lactobacillus species,

simplifying his findings for public consumption by likening probiotics' digestive benefits to

those observed in ruminant animals consuming fibrous vegetation (Petrova et al., 2021).

In Japan, in the early 1930s, Shirota successfully isolated strains of intestinal bacteria from

healthy individuals, capable of surviving and passing through the gut (Tang and Zhao, 2019). He

used these strains to develop fermented milk products and tested their effects on patients. His

initial products, marketed under the name Shirota (later named Lactobacillus casei Shirota), were

introduced by the Yakult Honsha Company (Okuno, 2020).

Probiotics can be defined as living microorganisms administered in sufficient quantities to persist

in the intestinal ecosystem and confer beneficial health effects ( Sharifi-Rad et al., 2020). The term

"probiotics" was first coined by Lilly and Stillwell (1965) to describe substances secreted by one

microorganism that stimulate the growth of another (Lokhande et al., 2018). Parker (1974)
proposed that probiotics are organisms and substances contributing to intestinal microbial

balance (Sampio et al., 2022). The Food and Agriculture Organization of the United

Nations/World Health Organization (FAO/WHO, 2001), endorsed by the International Scientific

Association for Probiotics and Prebiotics (Sampio et al., 2022), defined probiotics as live

microorganisms that, when administered in adequate amounts, confer health benefits on the host

(Sampio et al., 2022).

2.2 Common microbes used as probiotics

The microbes used as Probiotics represent different types such as bacteria, yeast or mold (Sen

and Mansell, 2020. However, there are more common species of each such as: 1 – Bacteria: (i)

Lactobacillus: acidophilus, sporogenes, plantarum, rhamnosum, delbrueck, reuteri, fermentum,

lactus, cellobiosus, brevis, casei, farciminis, paracasei, gasseri, crispatus; (ii) Bifidobacterium:

bifidum, infantis, adolescentis, longum, thermophilum, breve, lactis, animalis; (iii)

Streptococcus: lactis, cremoris, alivarius, intermedius, thermophilis, diacetylactis; (iv)

Leuconostoc mesenteroides; (v) Pediococcus; (vi) Propionibacterium; (vii) Bacillus; (viii)

Enterococcus; (ix) Enterococcus faecium; 2 – Yeast and molds: Saccharomyces cerevisiae,

Saccharomyces bourlardii, Aspergillus niger, Aspergillus oryzue, Candida pintolopesii,

Sacaromyces boulardii (Amara and Shibl, 2015).

2.3 Mechanism of action of probiotics

Some of the beneficial effects of probiotic consumption encompass:

- Enhancing intestinal tract health by regulating microbiota and fostering immune system

development and stimulation (Marandula et al., 2015).

- Synthesizing and improving the bioavailability of nutrients (Souri and Hatamian, 2019).

- Alleviating symptoms of lactose intolerance and mitigating the risk of certain diseases (Deng et

al., 2015).

Various mechanisms have been proposed to elucidate the advantageous impacts of probiotics.

These mechanisms entail modifying gut pH, antagonizing pathogens through the production of

antimicrobial compounds, competing for pathogen binding and receptor sites, nutrients, and

growth factors, stimulating immunomodulatory cells, and producing lactase (Palai et al., 2020).

Probiotics target specific actions and are probiotic-dependent, with different bacterial strains

potentially differing in their health effects ( Llewellyn and Foey, 2017). Additionally, the

mechanisms underlying probiotic effects may involve multifactorial processes and depend on

each probiotic strain's specific functions affecting the host's health. Considering their potential

targets, probiotics could be tailored and utilized in specific diseases based on their characteristics

and health-promoting effects (Plaza-Diaz et al., 2019).

Distinct levels of host-microbe interaction are discernible:

- Microbe-gut epithelium interaction involves adhesion to mucosal and epithelial cells,

stimulating mucus secretion, enhancing the production of defensive molecules such as mucins,

bolstering barrier function, innate immune function, reducing the secretory and inflammatory

consequences of bacterial infection, and improving gut motility (Liu et al., 2023).

- Microbe-immune system interaction entails immune modulation and the regulation of immune

responses beyond the gut (Lunjani et al., 2021).

- Microbe-microbe interaction involves modifying microbiota to suppress and inhibit pathogens,

preventing adhesion, establishment, and/or replication of pathogens in the gastrointestinal tract,

secretion of antimicrobial substances and compounds, competing for nutrients necessary for

pathogen survival, and anti-toxin effects (Caruana and walper, 2020).

Several proposed health effects of probiotics encompass the normalization of microbiota,

modulation of immune response, and metabolic functions (Sánchez et al., 2017).

Fig 2: Beneficial effects of probiotics on human health (Sánchez et al., 2017).

The advances in understanding these mechanisms of action and microbe-microbe interaction are

detailed below:

i. Adhesion

Adhesion to the intestinal mucosa is deemed a prerequisite for colonization and is crucially

related to strains' ability to modulate the immune system ( Nishiyama et al., 2016). Thus, adhesion

has been a primary selection criterion for new probiotic strains. Various intestinal mucosa

models have been utilized to evaluate probiotics' adhesive ability, with adhesion to human

intestinal mucus being widely employed and showing good correlations with other models.

Adhesion levels of probiotic and pathogen strains exhibit significant variability and depend on

each strain, species, and genus. However, high adherence ability in one strain does not always

guarantee in vivo persistence and protective effects, necessitating validation through studies in

animal models and humans (Byakika et al., 2019). Specific probiotics have been shown to

competitively inhibit the adhesion of pathogens such as Salmonella, Escherichia coli, Listeria

monocytogenes, Staphylococcus aureus, Bacteroides vulgatus, and Clostridium difficile, as well

as displace them. It is generally considered that probiotic strains inhibit pathogenic bacteria
attachment via steric hindrance at enterocyte pathogen receptors. Additionally, proteinaceous

components are involved in probiotic strains' adhesion to intestinal cells ( Monteagudo-Mera et al.,

2019). Recent reports demonstrate that all probiotic strains and combinations tested exhibit

abilities to inhibit, displace, and compete with pathogens. However, the high specificity of these

processes underscores the importance of characterizing strains' properties to select the most

effective strain combinations to prevent or treat infection by specific pathogens (Helmy and

Parang, 2023).
Fig 3: Interactions pathogen–receptor or toxin–receptor with probiotics. 'Probiotic' strain can

bind and neutralize toxins in the gut lumen or interfere with the adherence of pathogens to the

intestinal epithelium (Kumar Bajaj et al., 2015).

ii. Antimicrobial Substances

Antimicrobial metabolites produced by lactic acid bacteria can be categorized into low molecular

mass compounds (below 1,000 Da), such as organic acids, and antimicrobial proteins termed

bacteriocins (>1,000 Da) (Fen, 2016). The acids secreted during the fermentative metabolism of
carbohydrates by probiotics are considered the primary antimicrobial compounds responsible for

their inhibitory activity against pathogens (Monika et al., 2021). Bacteriocins exhibit bactericidal

activity against bacterial species closely related to the producer species. Probiotics have shown

antagonistic effects against pathogens belonging to various genera (Fijan, 2023).

iii. Immunomodulation

Recent studies indicate that specific probiotics' intake can effectively prevent and repair

intestinal damage by interacting with the mucosa-associated lymphoid tissue (Wang et al., 2021).

Probiotics can stimulate and regulate natural and acquired immune responses, impacting various

health conditions (Maldonado et al., 2019). They can bind to receptors on epithelial cells,

inducing humoral and cellular immune responses directed toward anti-inflammatory and pro-

inflammatory directions. The induced response varies among strains and species, with increasing

evidence suggesting that some probiotics can sufficiently stimulate a protective immune

response to enhance resistance to microbial pathogens (Giorgetti et al., 2015). Different strains of

probiotics may have varying effects on the immune system, influenced by dose and host immune

status. Probiotics may mediate these effects by inhibiting damage to intestinal cell junctions,

improving cell growth and survival, inducing mucin secretion, decreasing bacterial adhesion, and

secreting repair factors and nutrients (Guu et al., 2022).

CHAPTER THREE

3.1 Benefits of Probiotics

Reduction of Inflammation in the Intestines

Inflammation in the gut can result from an imbalance of bacteria or from irritants like certain

foods or medications (Dargahi et al., 2019). Probiotics help to modulate the immune response,

thereby reducing unnecessary inflammation in the intestines (Yousefi et al., 2019). This can be

especially beneficial for individuals with inflammatory bowel diseases, such as Crohn’s disease

or ulcerative colitis (Wehhamp et al., 2016).

Enhancement of the Immune System Function

Probiotics also bolster the body’s natural defenses (Ashaolu, 2020). They stimulate the

production of immune cells, such as lymphocytes and antibodies, preparing the body to fend off

potential pathogens (McComd et al., 2019). By enhancing the immune response, probiotics

contribute to overall health, reducing the susceptibility to common illnesses like colds or the flu

(Lehtoranta, 2021).

Aiding Digestion and Nutrient Absorption

Probiotics play a pivotal role in breaking down complex food particles, enabling efficient

digestion (Liu et al., 2019). This process ensures that essential nutrients from our diet, such as

vitamins and minerals, are effectively absorbed into the bloodstream (Zohoori, 2020). As a

result, the body receives the necessary nutrients for its various functions, enhancing overall

health (Zohoori, 2020).

Combating Harmful Bacteria and Infections

The gut is continuously exposed to various microorganisms, some of which can be harmful

(Browne et al., 2017). Probiotics actively compete with these harmful bacteria for space and
nutrients, effectively suppressing their growth. They reduce the risk of infections, including

those that can cause diarrhea or other gastrointestinal disturbance (Makomane et al., 2018).

Detoxifies the body

Over time, various toxins and pollutants, including heavy metals, can build up in the body. This

may lead to health issues such as weight gain, skin issues, hair problems, a weak immune

system, and gastrointestinal difficulties (Sardar et al., 2013).

Probiotics can aid the body in recovering from toxins by encouraging the growth of beneficial

bacteria in the gut microbiome. Furthermore, they aid in eliminating waste products by binding

and flushing out some harmful elements (Anee et al., 2021).

Certain probiotics have been known to bind and neutralize heavy metals such as lead, mercury,

and cadmium. Furthermore, they may increase the production of detoxifying enzymes that help

remove these toxins from the body (Bist and Choudhary, 2022).

Gut health is vital to your overall health. With the right probiotics from food or from dietary

supplements, you can gain the many benefits of better gut health (Kerry et al., 2018).

CHAPTER FOUR

4.1 CLINICAL APPLICATIONS AND MANAGEMENT OF PROBIOTICS WITH GUT

HEALTH
The primary clinical focus regarding probiotics' application has centered on preventing and

treating gastrointestinal infections, as well as managing infections caused by pathogenic

microorganisms such as H. pylori, E. coli, Salmonella, and Clostridium (S tavropoulou et al., 2020).

Deviations in microbiota have been linked to an increased risk of specific diseases like acute

gastroenteritis, atopic diseases, obesity, and even autism (Ihekweazu and Versalovic, 2018).

Thus, the rationale for probiotic therapy lies in modulating imbalanced indigenous microbiota.

Over the past few decades, numerous studies have evaluated probiotic microorganisms with

diverse formulas and specific purposes for disease prevention or treatment. Pathogens may

disrupt intestinal permeability, while probiotic strains could prevent damage, repair mucosal

integrity, increase epithelial resistance against pathogens, and induce cell proliferation (Gou et

al., 2022). Additionally, certain probiotic strains have exhibited protective effects against

conditions such as acute diarrhea, rotavirus diarrhea, antibiotic-associated diarrhea, Helicobacter

pylori infection, and alleviating symptoms of gastrointestinal diseases like irritable bowel

syndrome (Varankovich et al., 2015).

Regarding Helicobacter pylori infection, it is a Gram-negative spiral-shaped, micro-aerophilic

bacterium that colonizes the human gastric mucosa (Rahimkhai et al., 2019). This microorganism

is a specific inhabitant of the human stomach, prevalent in 70–90% of the population in

developing countries and 25–50% in developed countries (Alexander et al., 2021). Urease, a

significant product produced by H. pylori, hydrolyzes urea to ammonium, increasing the

stomach's pH, and thus facilitating colonization (Marcus and Scaott, 2024). Eradicating H. pylori

from the stomach typically requires a combination of therapies, including antibiotics (e.g.,

amoxicillin, clarithromycin, or nitroimidazoles) alongside acid suppression drugs (proton pump

inhibitors or H2-receptor antagonists) in triple or quadruple combinations. However, treatment

aimed at H. pylori eradication may disturb ecological balance, leading to the suppression of

normal microbiota and the emergence of antibiotic-resistant microbes (Piscione et al., 2021).

Several in vitro and in vivo studies on probiotics' role in treating H. pylori infections have shown

that probiotic strains can inhibit H. pylori growth or attachment through organic acid production,

antimicrobial substances of proteinaceous origin, competitive inhibition for binding sites to

mucus-producing cells, and immunomodulation. Notably, Lactobacillus salivarius has been

observed to inhibit H. pylori colonization, with post-H. pylori implantation administration of L.

salivarius eliminating H. pylori colonization in mice. Clinical studies have explored and reported

the potential use of probiotics as a supplement to antibiotic therapy for H. pylori. The

incorporation of probiotics resulted in reduced antibiotic side effects, enhanced patient adherence

to prescribed therapy, and elevated H. pylori eradication rates (Barishnikova te al., 2023).

However, no study provided evidence of complete eradication of H. pylori infection through

probiotic treatment. Nonetheless, prolonged consumption of probiotics may offer benefits for H.

pylori infection in humans, particularly by mitigating the risk of conditions linked to significant

gastric inflammation (Chakravarty and Gaur, 2019).

Diarrhea

The most well-supported health benefit of probiotics is their capacity to diminish the occurrence

or duration of various types of diarrhea (Sharifi-Rad et al., 2020). Research predominantly

concentrates on treating acute infectious diarrhea in children. Controlled clinical trials have

demonstrated the efficacy of specific strains such as Lactobacillus GG, Lactobacillus reuteri,

Lactobacillus casei, Saccharomyces boulardii, and various Bifidobacterium strains in reducing

the severity and duration of acute diarrhea (McFarland, 2021). Moreover, these probiotics have

shown effectiveness in managing other forms of diarrhea, including traveler's diarrhea and
rotavirus-induced diarrhea in young children. Administering probiotics alongside rehydration

therapy has been associated with shortening the duration of diarrhea in children by

approximately one day. Meta-analyses confirm the safety and efficacy of these probiotics (Li et

al., 2021).

Probiotic strains have also been evaluated for their potential in preventing or treat diarrhea

triggered by enteropathogens like E.s coli, Shigella, and Salmonella, which are major causes of

traveler's diarrhea, accounting for approximately 80% of cases with identified pathogens (Iqbal

et al., 2021). The most compelling evidence for beneficial effects comes from studies utilizing

specific strains like Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 for both

prevention and treatment of acute diarrhea (Wolvers et al., 2010). Furthermore, for infants and

young children suffering from severe diarrhea due to rotavirus infection, the combination of

rehydration with probiotic strains has shown promise in reducing the duration of the illness

(Wolvers et al., 2010).

Several clinical trials have indicated that fermented milk containing the probiotic Lactobacillus

casei DN 114 001 can diminish the severity and duration of acute diarrhea in young children (do

Carmo et al., 2018). Research has demonstrated that administering Lactobacillus GG in an oral

rehydration solution to children with acute diarrhea leads to a shorter duration of the illness

(Escribano et al., 2018). Moreover, the risk of developing diarrhea and rotavirus infection was

reduced in children who received a formula supplemented with bifidobacteria ( Escribano et al.,

2018). Probiotics have proven beneficial in preventing acute diarrhea in infants hospitalized with

chronic diseases. Supplementation of infant formula with Bifidobacterium Bb12 and S.

thermophilus TH4 significantly lowered the incidence of diarrhea in hospitalized infants

pathogens (Iqbal et al., 2021). Similar results were observed in a placebo-controlled double-blind
study involving infants aged 1 to 36 months who received L. rhamnosus GG pathogens (Iqbal et

al., 2021).

Recent reports have highlighted the effectiveness of a high-potency probiotic preparation in

preventing and treating radiation-induced diarrhea in cancer patients. Both the probiotic

combination VLS#3 and a probiotic drink containing Lactobacillus casei DN-114 001 have been

shown to be effective in reducing the occurrence and severity of radiation-induced diarrhea

(Wang et ail., 2016). Probiotics offer a simple, safe, and feasible approach to safeguarding cancer

patients against the risk of radiation-induced diarrhea, thereby opening up new avenues for their

use in managing various types of diarrhea linked to antibiotics and Clostridium difficile ( Petrariu

et al., 2024). There is evidence that certain probiotic strains have protective properties.

especially against diarrhea caused by Clostridium difficile and diarrhea brought on by antibiotics

(Petrariu et al., 2024). Antibiotic-associated diarrhea (AAD), which affects 5–25% of patients, is a

frequent side effect of antimicrobial drug therapy (Kopacz et al., 2022).

It has been demonstrated that probiotics given in addition to antibiotic therapy reduce the

incidence of antibiotic-associated diarrhea in both adults and children. Numerous strains, such as

Lactobacillus, Bifidobacterium, and Streptococcus, have been studied.

Allergic Disease
Allergy refers to a hypersensitivity reaction initiated by immunologic mechanisms, which can be

classified into IgE-mediated or non-IgE-mediated allergy (Anvari et al., 2019).

Abnormalities in the microbiota have been linked to the development of allergic diseases ( Peroni

et al., 2020). Infants who develop atopy often exhibit a reduced ratio of bifidobacteria to

clostridia. Allergic individuals tend to have a higher colonization of Clostridium and

Staphylococcus bacteria and lower levels of Enterococcus and Bifidobacterium compared to

non-allergic individuals (Boyarchuk et al., 2019). Changes in gut microbiota composition may

precede the development and manifestation of atopic diseases. Early colonization with

Escherichia coli has been associated with a higher risk of developing eczema, while colonization

with Clostridium difficile has been linked to eczema, recurrent wheezing, and allergic

sensitization in infancy (Melli et al., 2016). The hygiene hypothesis suggests that reduced

microbial exposure in early life leads to an increased risk of atopy and fewer infections during

childhood. Recent studies have reported differences in microbiota between allergic and healthy

infants in regions with varying allergy prevalence (Peroni et al., 2020). Probiotic bacteria may

counterbalance these microbiota changes. Positive clinical effects of probiotics in preventing and

treating atopic diseases have been documented. L. rhamnosus GG has been shown to prevent

atopic dermatitis in randomized, controlled trials. Administration of L. rhamnosus GG to

pregnant women for four weeks before delivery, followed by supplementation to newborns at

high risk of allergy for six months, resulted in a significant reduction in early atopic disease. This

study demonstrates the potential of probiotic microorganisms to modulate the immune response

and prevent allergic diseases (Elsami et al., 2020). In other clinical studies, infants allergic to

cow’s milk and those with atopic dermatitis experienced relief through the ingestion of probiotic

strains such as L. rhamnosus GG and B. lactis Bb12. However, no beneficial effects were
observed in adolescents with pollen allergy. In additional studies, L. rhamnosus GG was

combined with other probiotic strains, such as L. rhamnosus LC705, B. breve Bb99, and P.

freudenreichii subsp. shermanii JS, to assess their impact on the cumulative incidence of allergic

diseases (Fong et al., 2022). This study, involving 925 subjects followed up over two years,

found no effect on the overall incidence of allergic diseases, but it did significantly prevent

atopic eczema. Furthermore, several well-designed studies have provided evidence that specific

strains of probiotics can be somewhat effective in treating established atopic eczema with

intestinal involvement (Marras et al., 2021).

Cancer

Colorectal cancer (CRC) ranks as the second most common cause of cancer-related deaths, with

the Western diet playing a significant role in its risk. CRC arises from the abnormal proliferation

of epithelial cells in the colon or rectum (Yang et al., 2020). Current treatments, including

chemotherapy, radiotherapy, and surgery, pose high risks of complications and are not always

successful, underscoring the need for new treatment approaches. Various sources of evidence

suggest a potential involvement of the colonic microbiota in CRC etiology, prompting intense

interest in factors capable of modulating gut microbiota and their metabolism (Raskov et al.,

2017). The consumption of probiotics, prebiotics, or their combination (synbiotics) emerges as a

novel therapeutic option, as they work to alter intestinal microbiota by boosting beneficial

bacteria concentrations and reducing pathogenic microorganism levels. This strategy inhibits

neoplasia development and progression through mechanisms such as decreased intestinal

inflammation, enhanced immune function, anti-tumorigenic activity, binding to potential food

carcinogens (including meat product toxins), and reduction in bacterial enzymes like beta-

glucuronidase, which hydrolyze precarcinogenic compounds (Cutone et al., 2020).

Several experimental animal studies have clearly demonstrated the protective effect of probiotics

such as certain Lactobacillus and Bifidobacterium strains, or the combination of prebiotics and

probiotics, on the establishment, growth, and metastasis of transplantable and chemically

induced tumors (Fong et al., 2020). However, human intervention trials to confirm these findings

are inherently challenging due to the natural course of the disease (difficulty in selecting high-

risk subjects and the need for long-term follow-up) (Fong et al., 2020).

Obesity

Obesity stands as one of the foremost public health challenges today, with its impact being most

profound in children, contributing significantly to adult morbidity (Sneha, 2018). Metabolic

complications associated with childhood obesity often persist into adulthood, elevating the risk

of type 2 diabetes and early cardiovascular diseases ( Weihrauch-Blüher et al., 2019). Risk factors

for infant obesity include dietary habits, low socioeconomic status, maternal obesity, rapid

infancy weight gain, and reduced physical activity. Additionally, some reports suggest that gut

microbiota play a crucial role in energy disposal and storage in adipocytes. A recent study

indicated that infants with high levels of Bifidobacterium and low levels of Staphylococcus may

be shielded from excessive weight gain later in life (Saturio et al., 2021). The prevalence of

Bifidobacterium genus and species in breast-fed infants suggests a potential reason why

breastfed babies have a lower risk of obesity later in life. These findings offer new avenues for

obesity prevention since obese children often transition into obese adults, and maternal obesity

can contribute to infant over-nourishment, programming adult size and health with an increased

obesity risk later in life (Memela, 2017). Moreover, studies have shown how diets rich in protein

and/or low in carbohydrates or fats can alter microbial composition and activity in the large

intestine, thereby affecting gut health (Memela, 2017). Modifying microbiota through probiotic
use may offer new preventive and therapeutic approaches to reducing the risk of overweight and

obesity (Cerdó et al., 2019).

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) manifests with abdominal pain, bloating, and changes in bowel

habits, without any overt mucosal abnormality and flatulence (Defrees and Bailey, 2017). In a

double-blind clinical trial involving patients with bloating-predominant IBS, the probiotic

mixture VSL#3 reduced flatulence scores (Cheng et al., 2020). Probiotics offer potential benefits

in managing IBS symptoms through various mechanisms, including the augmentation of mucosal

TGF- and IL-10 levels and the reduction of pro-inflammatory cytokines such as IL-12 and

interferon (IFN) (Simon et al., 2021). Several studies in adults have demonstrated the efficacy of

B. infantis, L. rhamnosus GG, and combinations of different probiotics like L. rhamnosus GG, L.

rhamnosus LC705, B. breve Bb99, and Propionibacterium freudenreichii JS in alleviating IBS

symptoms (Simon et al., 2021). In infants, L. rhamnosus GG reduced perceived abdominal

distension but not abdominal pain (Roy and Dhaneshar, 2023). Other placebo-controlled trials

have shown relief from abdominal bloating in IBS patients treated with VSL#3 or/and

Lactobacillus plantarum, as well as pain reduction with L. plantarum or L. rhamnosus GG (Chen

et al., 2020).

Inflammatory Bowel Disease

 Inflammatory bowel disease (IBD) represents a chronic and recurrent inflammation that

typically affects the colon or small intestine, encompassing conditions such as ulcerative colitis,

pouchitis, and Crohn's disease (M’Koma, 2022). Although the etiology of IBD remains unclear,

genetic predisposition and alterations in microbiota are implicated. Abnormal immune reactions

to the endogenous microbiota are observed in patients with inflammatory bowel diseases, with

higher levels of specific bacteria like Bacteroides attached to epithelial cells compared to healthy

individuals (Qui et al., 2022). Microbiota instability has been noted in individuals with irritable

bowel issues compared to healthy adults (Qui et al., 2022). Therapeutic manipulation of the

gastrointestinal microbiota using probiotics, either alone or in various combinations, is being

explored as a treatment option (Hansen and Sartor, 2015). Evaluation of the use of probiotic

strains and combinations in the treatment of inflammatory bowel diseases, although limited

studies are available for IBD in general, as well as for ulcerative colitis, chronic pouchitis, and

Crohn’s disease (Oka and Sartor, 2020).

 CHAPTER FIVE

Conclusion

Probiotics play a significant role in maintaining gut health by modulating the composition and

function of the intestinal microbiota. Evidence from numerous studies suggests that probiotics

offer various benefits, including the prevention and management of gastrointestinal disorders

such as diarrhea, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD).

Additionally, probiotics have been implicated in supporting immune function, reducing

inflammation, enhancing nutrient absorption, and even exerting positive effects on mental health

through the gut-brain axis. While the field of probiotics holds promise, more research is needed

to better understand their mechanisms of action, optimal dosages, specific strains for different

conditions, and long-term effects.

Recommendations:

1. Dietary Diversification: Encourage a diet rich in probiotic-containing foods such as yogurt,

kefir, kimchi, sauerkraut, and other fermented foods to promote gut health naturally.

Additionally, incorporating prebiotic-rich foods like fruits, vegetables, and whole grains can

provide nourishment for beneficial gut bacteria.

2. Evidence-Based Supplementation: Consider probiotic supplementation for individuals with

specific gastrointestinal conditions, such as antibiotic-associated diarrhea, IBS, and IBD, under

the guidance of a healthcare professional. Choose probiotic supplements backed by scientific

evidence and containing strains proven effective for the intended purpose.
3. Tailored Approach: Recognize that the efficacy of probiotics may vary depending on factors

such as the individual's microbiome composition, health status, and the presence of underlying

conditions. Adopt a personalized approach to probiotic use, considering the unique needs and

circumstances of each individual.

4. Clinical Research: Support and conduct further research to elucidate the mechanisms of action

of probiotics, identify optimal strains and dosages for different health conditions, and assess their

long-term safety and efficacy. Well-designed clinical trials, including randomized controlled

trials, are essential to strengthen the evidence base and inform clinical practice.

5. Education and Awareness: Promote public awareness about the potential benefits and

limitations of probiotics in maintaining gut health. Educate healthcare professionals, patients,

and the general public about probiotic use, emphasizing evidence-based recommendations and

dispelling misconceptions.

6. Regulatory Oversight: Advocate for regulatory oversight to ensure the quality, safety, and

efficacy of probiotic products. Strengthen regulations governing probiotic labeling, marketing

claims, and product quality standards to protect consumers and promote informed decision-

making.
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