**3.4 Gut microbiome and pulmonary health**

Infectious diseases of the respiratory tract including pneumonia and influenza result in deaths of approximately 3.25 million people annually [99]. The majority of the therapies being used currently are suboptimal because the problems of efficiency, toxicity and antibiotic resistance are difficult to overcome [100]. Most of the respiratory tract infections represent failure of host's immune defense. Recently, it was suggested that gut microbiota plays a crucial role in the initiation and adaptation of the immune response in other distal mucosal sites including lungs. Therefore, it is of interest to understand the underlying mechanisms that regulate the interplay between lung defense and gastrointestinal tract and how this interaction aids in achieving optimal lung health.

#### *3.4.1 Asthma and allergies*

An abnormal T-helper type 2 (Th2) cell responses is often associated with asthma and allergies. The Th2 cells are recognized by their ability to synthesize inflammatory cytokines including IL-13, IL-9, IL-5 and IL-4 [101] Evidence suggests that the development of allergic diseases in lung is directly affected by alteration in gut immune response [65]. In fact, a single oral dose of *Candida albicans* administered to antibiotic treated mice resulted in dysbiosis, i.e., an altered composition of the gut microbiome. These treated mice exhibited more CD4 cell mediated inflammation response in lung after aerosol administration of an allergen in comparison to those mice having normal intestinal flora [102], suggesting that an immunological predisposition to respiratory allergies can be facilitated by an altered gut microbiome. There is also an increasing interest in understanding the role of Th9 and Th17 cells in the development of asthma and allergies.

#### *3.4.2 Viral and bacterial respiratory infections*

Gut microbiota also plays a critical role in the immune response to respiratory tract viral infections like influenza. In infected mice, the CD8 and CD4 T cell subpopulations are directly influenced by the intestinal microbiota [103]. It has also been suggested that an intact intestinal microbiota is necessary for the expression of pro-inflammatory cytokines including pro-IL-18 and pro-IL-1β, which are essential for clearance of influenza [104]. This indicates that microbial signals are provided by gut microbiota which are crucial for the shaping and priming the immune response to viral pneumonia.

Similar findings regarding the role of gut microbiome in immune response to respiratory bacterial infections have also been observed in germ-free mice. These mice were found to be more susceptible to pulmonary infection caused by bacterial pathogen *Klebsiella pneumonia*, showing increased levels of IL-10 and suppressed recruitment of neutrophil that allows dissemination and growth of pathogens [105].

#### **3.5 Gut microbiome and pregnancy**

All systems of the body including maternal microbiome are affected by pregnancy. Changes in gut and vaginal microbiome during gestation are of particular significance because during vaginal delivery there is vertical transmission of microbes to the newborn [106–108]. During pregnancy the vaginal microbiota composition changes throughout the gestation period. In addition to vaginal microbiome, the maternal intestinal microbiome also undergoes change during pregnancy. It has been reported that bacterial diversity decreases in women as the pregnancy progresses [107]. Particularly, the ratio of pro-inflammatory *Proteobacteria,* which includes the *Streptococcus* genus and *Enterobacteriaceae* family, reduces during first and third trimester, while an increase in the anti-inflammatory *Faecalibacterium prausnitzii* occurs during these trimesters of pregnancy. These changes in microbiome are independent of body weight during pregnancy, diet, antibiotic use and gestational diabetes, suggesting the association of these changes with normal physiological pregnancy-related alteration in maternal immune and endocrine systems [109].

The consequences of changes in maternal vaginal and gut microbiota on mother health are not clear; however, the gestational changes in fecal and vaginal microbiota are considered to be important for the adaptive response necessary for protection as well as to promote the fetus health. These changes also help in providing a particular microbial inoculum to the newborn at birth before its exposure to other environmental microbes. Also the microbial communities' composition in maternal vagina and gut are not independent of each other. In fact, in pregnant women of 35–37 weeks of gestation most of bacteria, including species of *Bifidobacterium* and *Lactobacillus*, are common between vagina and rectum [110].

Some research studies reported that shift in gut microbiota of mother during pregnancy may be an adaptive response for the mother and newborn health. In mice, an increase in the gut bacteria associated with gestational age, promotes body weight gain indicating a co-evolution of these microbes with their hosts during pregnancy [107]. Moreover, during vaginal delivery, the vertical transmission of these maternal gut microbiomes to the neonate may help the newborn to get an immediate access to microbiota at birth [107, 111].

#### **4. Role of gut-microbiome in brain physiology**

Both extrinsic and intrinsic factors play an important role to regulate the development and maturation of the central nervous system (CNS) in humans. In germ-free and antibiotic-treated animals the physiology of the CNS can be affected by neurochemistry as well as by specific microbiota [112]. Evidences for interaction between neuropsychiatric and gastrointestinal pathology in humans have been reported in different psychiatric conditions including autism, depression and anxiety [113].

**185**

*Gut Microbiome: A New Organ System in Body DOI: http://dx.doi.org/10.5772/intechopen.89634*

**5.1 Physical or psychological stress**

impairment of the immune system [123, 124].

**5.2 Use of antibiotics**

The role of gut-brain interaction in the nervous system development is also recognized. Gut-brain axis actually establishes a relationship between gut-microbiota and their interaction with brain leading to changes in the status of the CNS. The dysbiosis in microbial species of the gut may lead to induce imbalance in host homeostasis, atypical immune signaling and ultimately progression of CNS diseases [114].

The permeable blood brain barrier (BBB) and functional lymphatic vessels residing in dura meningeal membrane may serve as a gateway for transmission of signals [115]. The exposure to several environmental factors can affect the generation of neurons during the development of the CNS [113]. It has been suggested that maternal-fetal interface permeability permits regulatory factors from the gut microbiota to stimulate Toll-like receptor 2 (TLR2) that helps to promote neural development of fetus and also impart its effects on cognitive function during adulthood [116]. The combination of microbial strains (especially the probiotic) can actively counteract the deficient neurogenesis which further strengthen the developmental link of microbiome to the hippocampal neuronal generation [117]. The brain-blood barrier (BBB) is a highly selective and semipermeable barricade that permits the passage of neutral, low molecular weight and lipidic soluble molecules [118]. In the development of the structural components and growth of vasculature, BBB requires arachidonic acid (AA) and decohexaenoic acid (DHA) which are provided as polyunsaturated fatty acids (PUFA) by gut microbiome [119]. It has been demonstrated that the restoration of BBB is possible in germ-free mice by colonization of

*Clostridium tyrobutyricum* that produce high level of butyrates [120].

**5. Impact of different environmental conditions on gut microbiome**

Physical or psychological stress, (ii) use of antibiotics, and (iii) diet (**Figure 2**).

The most important environmental factors that may lead to dysbiosis include (i)

Stress is usually defined as homeostasis disruption due to physical, psychological or environmental stimuli known as stressors leading to adaptive behavioral and physiological response in order to restore homeostasis [121]. The effect of both psychological and physical stress on gut microbiome is widely recognized and has been observed in both humans as well as animals [122]. Some research conducted in mice has shown that the microbial composition in the cecum was altered in response to the exposure of a social stressor by placing an aggressive male mouse into the cages of non-aggressive mice. Furthermore, the plasma concentration of stress hormones such as adrenocorticotropic hormone (ACTH) and corticosterone was found to be significantly higher in germ-free mice as compared to specific pathogen-free mice. In addition, several stressors including acoustic stress, self-control conditions and food deprivation have a negative impact on the gut microbiome resulting in the

It has been observed in both humans and animals that the treatment with antibiotics can result in a decreased population of beneficial bacteria including *Lactobacilli* and *Bifidobacteria* along with the increased population of potential pathogenic bacteria like *Clostridium difficile* and the pathogenic yeast *Candida albicans*. The GI symptoms for example diarrhea, abdominal pain, bloating as well as yeast infections may occur in response to microbial shifts or dysbiosis. However,

#### *Gut Microbiome: A New Organ System in Body DOI: http://dx.doi.org/10.5772/intechopen.89634*

*Parasitology and Microbiology Research*

response to viral pneumonia.

**3.5 Gut microbiome and pregnancy**

endocrine systems [109].

pro-inflammatory cytokines including pro-IL-18 and pro-IL-1β, which are essential for clearance of influenza [104]. This indicates that microbial signals are provided by gut microbiota which are crucial for the shaping and priming the immune

Similar findings regarding the role of gut microbiome in immune response to respiratory bacterial infections have also been observed in germ-free mice. These mice were found to be more susceptible to pulmonary infection caused by bacterial pathogen *Klebsiella pneumonia*, showing increased levels of IL-10 and suppressed recruitment of neutrophil that allows dissemination and growth of pathogens [105].

All systems of the body including maternal microbiome are affected by pregnancy. Changes in gut and vaginal microbiome during gestation are of particular significance because during vaginal delivery there is vertical transmission of microbes to the newborn [106–108]. During pregnancy the vaginal microbiota composition changes throughout the gestation period. In addition to vaginal microbiome, the maternal intestinal microbiome also undergoes change during pregnancy. It has been reported that bacterial diversity decreases in women as the pregnancy progresses [107]. Particularly, the ratio of pro-inflammatory *Proteobacteria,* which includes the *Streptococcus* genus and *Enterobacteriaceae* family, reduces during first and third trimester, while an increase in the anti-inflammatory *Faecalibacterium prausnitzii* occurs during these trimesters of pregnancy. These changes in microbiome are independent of body weight during pregnancy, diet, antibiotic use and gestational diabetes, suggesting the association of these changes with normal physiological pregnancy-related alteration in maternal immune and

The consequences of changes in maternal vaginal and gut microbiota on mother health are not clear; however, the gestational changes in fecal and vaginal microbiota are considered to be important for the adaptive response necessary for protection as well as to promote the fetus health. These changes also help in providing a particular microbial inoculum to the newborn at birth before its exposure to other environmental microbes. Also the microbial communities' composition in maternal vagina and gut are not independent of each other. In fact, in pregnant women of 35–37 weeks of gestation most of bacteria, including species of *Bifidobacterium* and

Some research studies reported that shift in gut microbiota of mother during pregnancy may be an adaptive response for the mother and newborn health. In mice, an increase in the gut bacteria associated with gestational age, promotes body weight gain indicating a co-evolution of these microbes with their hosts during pregnancy [107]. Moreover, during vaginal delivery, the vertical transmission of these maternal gut microbiomes to the neonate may help the newborn to get an

Both extrinsic and intrinsic factors play an important role to regulate the development and maturation of the central nervous system (CNS) in humans. In germ-free and antibiotic-treated animals the physiology of the CNS can be affected by neurochemistry as well as by specific microbiota [112]. Evidences for interaction between neuropsychiatric and gastrointestinal pathology in humans have been reported in different psychiatric conditions including autism, depression and anxiety [113].

*Lactobacillus*, are common between vagina and rectum [110].

immediate access to microbiota at birth [107, 111].

**4. Role of gut-microbiome in brain physiology**

**184**

The role of gut-brain interaction in the nervous system development is also recognized. Gut-brain axis actually establishes a relationship between gut-microbiota and their interaction with brain leading to changes in the status of the CNS. The dysbiosis in microbial species of the gut may lead to induce imbalance in host homeostasis, atypical immune signaling and ultimately progression of CNS diseases [114].

The permeable blood brain barrier (BBB) and functional lymphatic vessels residing in dura meningeal membrane may serve as a gateway for transmission of signals [115]. The exposure to several environmental factors can affect the generation of neurons during the development of the CNS [113]. It has been suggested that maternal-fetal interface permeability permits regulatory factors from the gut microbiota to stimulate Toll-like receptor 2 (TLR2) that helps to promote neural development of fetus and also impart its effects on cognitive function during adulthood [116].

The combination of microbial strains (especially the probiotic) can actively counteract the deficient neurogenesis which further strengthen the developmental link of microbiome to the hippocampal neuronal generation [117]. The brain-blood barrier (BBB) is a highly selective and semipermeable barricade that permits the passage of neutral, low molecular weight and lipidic soluble molecules [118]. In the development of the structural components and growth of vasculature, BBB requires arachidonic acid (AA) and decohexaenoic acid (DHA) which are provided as polyunsaturated fatty acids (PUFA) by gut microbiome [119]. It has been demonstrated that the restoration of BBB is possible in germ-free mice by colonization of *Clostridium tyrobutyricum* that produce high level of butyrates [120].
