The Human Microbiome in Early Life

Implications to Health and Disease

Omry Koren, Samuli Rautava, Omry Koren, Samuli Rautava

• Verlag: Academic Press
• Jahr: 2020
• ISBN:
  9780128180983
• Thema: Biowissenschaften
• Thema: Mikrobiologie

The Human Microbiome in Early Life: Implications to Health and Disease presents recent research advances that have highlighted the significance of early life, possibly beginning before birth, in the establishment of both the microbiome and its role in health and disease. The book reviews current knowledge on the origins of the human microbiota in early life, presents exposures which may disturb normal microbial colonization, and covers their implications to the risk of disease. Finally, emerging means to modify the early human microbiome to improve health are discussed.

• Examines the timeline of the human microbiome, from before conception to infancy, with an emphasis on clinical implications
• Evaluates the effort to understand not only the composition but also the origin of the microbiome
• Proves the emerging means to modify the human microbiome and particularly 'the first 1000 days of life' improve human health and prevent disease
• Generates resources to facilitate characterization of the human microbiota to further our understanding of how the microbiome impacts human health and disease

Section I

Pregnancy and fetal life

Outline

• Chapter 1 The microbiome in a healthy pregnancy
• Chapter 2 The microbiome and pregnancy complications
• Chapter 3 Microbial signatures of preterm birth
• Chapter 4 Prenatal origins of the infant gut microbiome

Chapter 1

The microbiome in a healthy pregnancy

Hadar Neuman¹ and Omry Koren², ¹1Zefat Academic College, Safed, Israel, ²2Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel

Abstract

The human microbiome plays fundamental roles in host metabolism, immunity, and overall health. In many disease states, the microbial composition is altered (dysbiosis), usually exacerbating the clinical condition. However, during pregnancy, the changes in the microbiome are essential for healthy pregnancy progression and outcome. Alterations in microbial compositions are evident in the gut, oral cavity, and the vagina of pregnant women. The microbial changes during pregnancy are correlated with and enhance the gestational immune, hormonal, and metabolic changes that occur during pregnancy, including weight gain. Understanding the extent of the changes in the microbiome that occur in healthy pregnancy and the full effects of the maternal microbiome on the offspring is expected to have an important impact when considering antibiotics and nutritional decisions during pregnancy.

Keywords

Microbiome; pregnancy; progesterone; hormones; immunity

Introduction

The human microbiome, comprising hundreds of microbial species residing within the human body, has been shown to have essential roles in promoting and maintaining health. These include effects on immunity, metabolism, and even involvement in the endocrine system and behavior.

Drastic changes to microbial composition and diversity are typically correlated with disease conditions and are termed dysbiosis. Such changes have been observed in autoimmune diseases, diabetes, obesity, and metabolic syndrome [1–4]. However, during healthy pregnancies, distinct changes are observed in the microbiome, some of which resemble the changes observed in disease states. This phenomenon is not coincidental, but rather essential for the progression of a healthy pregnancy. Thus pregnancy is unique as a positive and physiological example of dysbiosis. In this chapter, we will describe the overall microbial changes during pregnancy and relate these changes to their functional significance. The spectrum of functional effects ranges between influencing the maternal immune system, promoting weight gain, and altering metabolism. Pregnancy complications are correlated with additional distinct microbial alterations, emphasizing the potential roles of the microbiome in both healthy pregnancies, and in the case of complications (discussed in the following chapters). Finally, the maternal microbiome has clear effects on the offspring, as manifested by the initial infant microbiome, and the consequences of antibiotic exposure during gestation.

Understanding the functional changes in the pregnancy microbiome is important for obtaining a full picture of the physiological processes that occur during pregnancy, for evaluation of the state of the pregnancy, and for deciphering potential risk factors for the pregnant mother and developing fetus. It appears evident that the complex immune, hormonal, metabolic, and microbial alterations that occur during pregnancy are correlated with one another, forming a network of physiological processes.

The importance and roles of a healthy microbiome

In the healthy state, our microbiome includes highly diverse populations of bacteria residing in a variety of body sites and niches. These bacterial populations have different characteristics—some are aerobic, whereas others are anaerobic; they can thrive at a variety of pH values and within a range of nutritional milieus [5]. The bacterial populations are also greatly affected by immune and hormonal factors. This explains why the gut microbiota significantly differs from the vaginal or the oral one, why the microbial populations are not identical between individuals, and emphasizes the importance of rich populations of microbes adapting to the changing surroundings during dynamic homeostatic conditions. On a functional level, it is assumed that microbes residing in different body sites also serve different roles in maintaining overall health. While the gut microbiome may play the most essential roles regarding human metabolism, as well as affecting immunity and hormones, the microbiome of the skin, vagina, and oral cavity contributes directly to the immune system in its defense against outside pathogens [6].

The many metabolic roles of the microbiota include food digestion, fermentation of carbohydrates into short-chain fatty acids (SCFAs), digestion of proteins into amino acids, production of vitamins, and metabolism of drugs and xenobiotics [7]. The microbiota has also been implicated in lipid metabolism, conversion of bile acids, and breakdown of polyphenols.

The immunological roles of microbiota are numerous. They help form a barrier for repressing pathogens and modulate the host immune response by affecting both innate and adaptive immune system components [8]. The presence of the microbiota maintains a balance in the abundance of immune cell populations, such as Treg cells versus T helper 17 (TH17) cells [9]. Moreover, levels of pro-inflammatory cytokines have been shown to depend on the microbial composition.

Additional effects of the microbiome on their hosts include altering hormone levels and affecting brain function and behavior [10–12]. A close interplay between the microbiome and the host endocrine system has been described [13]. While host hormones affect the growth of certain bacteria and their function, bacteria can produce and modulate hormones influencing behavior, appetite, metabolism, gender, and immunity.

Similarly, the microbiome is both affected by the brain and can affect the brain development as well as impact appetite, emotions, stress response, cognition, and behavior, such as anxiety and aggression [14]. To this end, the gut microbiome has been shown to be altered in various psychiatric disorders including major depression, schizophrenia, and autism [13,15,16]. One potential mechanism for this effect is the capacity of gut microbiota to produce several human brain neurotransmitters [14]. Other components that might link the microbiome and behavior include hormones and immune parameters.

While alterations in microbiome are associated with developmental changes across our lifetime (e.g., from infancy to childhood, and later, old age), with dietary changes, and with other environmental factors, most divergence from steady-state microbial populations (dysbiosis) has been associated with disease states. Dysbiosis usually includes a decline in microbial diversity and may have long-term consequences leading to disease or enhancing a disease state. Examples of diseases associated with dysbiosis include obesity, inflammatory bowel disease, diabetes, and metabolic syndrome [3]. In fact, it has been suggested that almost all diseases are characterized by a perturbation of the healthy microbiome into an unbalanced diseased state, so that our overall fitness and health are closely intertwined with our microbiome composition [17].

Some of the microbial changes that occur during pregnancy may seem identical to those seen in disease states. However, in their precise developmental context, they do not lead to morbidity, but rather promote necessary functions, including a more flexible immune state and altered metabolism, and may therefore be considered beneficial.

The gut microbiome is altered during pregnancy

Pregnancy leads to dramatic changes in the gut microbiome. These alterations include a distinct reduction in bacterial diversity and richness within individuals (decreased α diversity), less similarity in microbial composition between different women (increased β diversity), and an increase in the bacterial load [18,19]. In addition, alterations in species abundance are observed, with some bacterial species being overrepresented and others being underrepresented as compared to the nonpregnant state [19].

Interestingly, most of the pregnancy-related microbial changes are seen at late stages of pregnancy, in the third trimester. This is also the time when other physiological parameters such as weight gain, insulin insensitivity, inflammation, and changes in hormonal levels reach a peak [20,21]. A recent study found that progesterone has a direct effect on the microbial composition, specifically increasing the richness of several species including Bifidobacterium in the gut microbial composition of women and mice during late pregnancy [22].

Some of the pregnancy-related microbial alterations seem to correlate with the metabolic state observed in late pregnancy. For example, there is a significant reduction in SCFA producers such as the butyrate-producing bacterium Faecalibacterium, similar to the depletion seen in metabolic syndrome patients [23]. On the oth...