Microbe Chain

1. Microbe Chain
2. Bacteria Chains

Jump to:
What is the microbiome?
How microbiota benefit the body
The role of probiotics
Can diet affect one’s microbiota?
Future areas of research

What is the microbiome?

Microbe Chain

Picture a bustling city on a weekday morning, the sidewalks flooded with people rushing to get to work or to appointments. Now imagine this at a microscopic level and you have an idea of what the microbiome looks like inside our bodies, consisting of trillions of microorganisms (also called microbiota or microbes) of thousands of different species. [1] These include not only bacteria but fungi, parasites, and viruses. In a healthy person, these “bugs” coexist peacefully, with the largest numbers found in the small and large intestines but also throughout the body. The microbiome is even labeled a supporting organ because it plays so many key roles in promoting the smooth daily operations of the human body.

Each person has an entirely unique network of microbiota that is originally determined by one’s DNA. A person is first exposed to microorganisms as an infant, during delivery in the birth canal and through the mother’s breast milk. [1] Exactly which microorganisms the infant is exposed to depends solely on the species found in the mother. Later on, environmental exposures and diet can change one’s microbiome to be either beneficial to health or place one at greater risk for disease.

The microbiome consists of microbes that are both helpful and potentially harmful. Most are symbiotic (where both the human body and microbiota benefit) and some, in smaller numbers, are pathogenic (promoting disease). In a healthy body, pathogenic and symbiotic microbiota coexist without problems. But if there is a disturbance in that balance—brought on by infectious illnesses, certain diets, or the prolonged use of antibiotics or other bacteria-destroying medications—dysbiosis occurs, stopping these normal interactions. As a result, the body may become more susceptible to disease.

• Microbes need nutrients for growth and they like to consume the same foods as humans. They can get into our food at any point along the food chain from ‘plough to plate’. Therefore great care must be taken at every stage of food production to ensure that harmful microbes are not allowed to survive and multiply.
• Short chain fatty acids (SCFA) are released as a result of fermentation. This lowers the pH of the colon, which in turn determines the type of microbiota present that would survive in this acidic environment. The lower pH limits the growth of some harmful bacteria like Clostridium difficile.

Organisms that make their own food are called primary producers and are always at the start of the food chain. Animals and micro-organisms like fungi and bacteria get energy and nutrients by eating other plants, animals and microbes.

How microbiota benefit the body

Microbiota stimulate the immune system, break down potentially toxic food compounds, and synthesize certain vitamins and amino acids, [2] including the B vitamins and vitamin K. For example, the key enzymes needed to form vitamin B12 are only found in bacteria, not in plants and animals. [3]

Sugars like table sugar and lactose (milk sugar) are quickly absorbed in the upper part of the small intestine, but more complex carbohydrates like starches and fibers are not as easily digested and may travel lower to the large intestine. There, the microbiota help to break down these compounds with their digestive enzymes. The fermentation of indigestible fibers causes the production of short chain fatty acids (SCFA) that can be used by the body as a nutrient source but also play an important role in muscle function and possibly the prevention of chronic diseases, including certain cancers and bowel disorders. Clinical studies have shown that SCFA may be useful in the treatment of ulcerative colitis, Crohn’s disease, and antibiotic-associated diarrhea. [2]

The microbiota of a healthy person will also provide protection from pathogenic organisms that enter the body such as through drinking or eating contaminated water or food.

Large families of bacteria found in the human gut include Prevotella, Ruminococcus, Bacteroides, and Firmicutes. [4] In the colon, a low oxygen environment, you will find the anaerobic bacteria Peptostreptococcus,Bifidobacterium, Lactobacillus, and Clostridium. [4] These microbes are believed to prevent the overgrowth of harmful bacteria by competing for nutrients and attachment sites to the mucus membranes of the gut, a major site of immune activity and production of antimicrobial proteins. [5,6]

The role of probiotics

If microbiota are so vital to our health, how can we ensure that we have enough or the right types? You may be familiar with probiotics or perhaps already using them. These are either foods that naturally contain microbiota, or supplement pills that contain live active bacteria—advertised to promote digestive health. Probiotic supplement sales exceeded $35 billion in 2015, with a projected increase to $65 billion by 2024. Whether you believe the health claims or think they are yet another snake oil scam, they make up a multi-billion dollar industry that is evolving in tandem with quickly emerging research.

Dr. Allan Walker, Professor of Nutrition at the Harvard Chan School of Public Health and Harvard Medical School, believes that although published research is conflicting, there are specific situations where probiotic supplements may be helpful. “Probiotics can be most effective at both ends of the age spectrum, because that’s when your microbes aren’t as robust as they normally are,” Walker explains. “You can influence this huge bacterial colonization process more effectively with probiotics during these periods.” He also notes situations of stress to the body where probiotics may be helpful, such as reducing severity of diarrhea after exposure to pathogens, or replenishing normal bacteria in the intestine after a patient uses antibiotics. Still, Walker emphasizes that “these are all circumstances where there’s a disruption of balance within the intestine. If you’re dealing with a healthy adult or older child who isn’t on antibiotics, I don’t think giving a probiotic is going to be that effective in generally helping their health.”

Because probiotics fall under the category of supplements and not food, they are not regulated by the Food and Drug Administration in the U.S. This means that unless the supplement company voluntarily discloses information on quality, such as carrying the USP (U.S. Pharmacopeial Convention) seal that provides standards for quality and purity, a probiotic pill may not contain the amounts listed on the label or even guarantee that the bacteria are alive and active at the time of use.

Can diet affect one’s microbiota?

In addition to family genes, environment, and medication use, diet plays a large role in determining what kinds of microbiota live in the colon. [2] All of these factors create a unique microbiome from person to person. A high-fiber diet in particular affects the type and amount of microbiota in the intestines. Dietary fiber can only be broken down and fermented by enzymes from microbiota living in the colon. Short chain fatty acids (SCFA) are released as a result of fermentation. This lowers the pH of the colon, which in turn determines the type of microbiota present that would survive in this acidic environment. The lower pH limits the growth of some harmful bacteria like Clostridium difficile. Growing research on SCFA explores their wide-ranging effects on health, including stimulating immune cell activity and maintaining normal blood levels of glucose and cholesterol.

Foods that support increased levels of SCFA are indigestible carbohydrates and fibers such as inulin, resistant starches, gums, pectins, and fructooligosaccharides. These fibers are sometimes called prebiotics because they feed our beneficial microbiota. Although there are supplements containing prebiotic fibers, there are many healthful foods naturally containing prebiotics. The highest amounts are found in raw versions of the following: garlic, onions, leeks, asparagus, Jerusalem artichokes, dandelion greens, bananas, and seaweed. In general, fruits, vegetables, beans, and whole grains like wheat, oats, and barley are all good sources of prebiotic fibers.

Be aware that a high intake of prebiotic foods, especially if introduced suddenly, can increase gas production (flatulence) and bloating. Individuals with gastrointestinal sensitivities such as irritable bowel syndrome should introduce these foods in small amounts to first assess tolerance. With continued use, tolerance may improve with fewer side effects.

If one does not have food sensitivities, it is important to gradually implement a high-fiber diet because a low-fiber diet may not only reduce the amount of beneficial microbiota, but increase the growth of pathogenic bacteria that thrive in a lower acidic environment.

Probiotic foods contain beneficial live microbiota that may further alter one’s microbiome. These include fermented foods like kefir, yogurt with live active cultures, pickled vegetables, tempeh, kombucha tea, kimchi, miso, and sauerkraut.

Future areas of research

The microbiome is a living dynamic environment where the relative abundance of species may fluctuate daily, weekly, and monthly depending on diet, medication, exercise, and a host of other environmental exposures. However, scientists are still in the early stages of understanding the microbiome’s broad role in health and the extent of problems that can occur from an interruption in the normal interactions between the microbiome and its host. [7]

Some current research topics:

• How the microbiome and their metabolites (substances produced by metabolism) influence human health and disease.
• What factors influence the framework and balance of one’s microbiome.
• The development of probiotics as a functional food and addressing regulatory issues.

Specific areas of interest:

• Factors that affect the microbiome of pregnant women, infants, and the pediatric population.
• Manipulating microbes to resist disease and respond better to treatments.
• Differences in the microbiome between healthy individuals and those with chronic disease such as diabetes, gastrointestinal diseases, obesity, cancers, and cardiovascular disease.
• Developing diagnostic biomarkers from the microbiome to identify diseases before they develop.
• Alteration of the microbiome through transplantation of microbes between individuals (e.g., fecal transplantation).

Related

1. Ursell, L.K., et al. Defining the Human Microbiome. Nutr Rev. 2012 Aug; 70(Suppl 1): S38–S44.
2. den Besten, Gijs., et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013 Sep; 54(9): 2325–2340.
3. Morowitz, M.J., Carlisle, E., Alverdy, J.C. Contributions of Intestinal Bacteria to Nutrition and Metabolism in the Critically Ill. Surg Clin North Am. 2011 Aug; 91(4): 771–785.
4. Arumugam, M., et al. Enterotypes of the human gut microbiome. Nature. 2011 May 12;473(7346):174-80.
5. Canny, G.O., McCormick, B.A. Bacteria in the Intestine, Helpful Residents or Enemies from Within. Infect and Immun. August 2008 vol. 76 no. 8, 3360-3373.
6. Jandhyala, S.M. Role of the normal gut microbiota. World J Gastroenterol. 2015 Aug 7; 21(29): 8787–8803.
7. Proctor, L.M. The Human Microbiome Project in 2011 and Beyond. Cell Host & Microbe. Volume 10, Issue 4, 20 October 2011, pp 287-91.

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by Molly Sargen

figures by Molly Sargen and Nicholas Lue

Microbes (also known as microorganisms) are everywhere: on surfaces we touch, in the air we breathe, and even inside us. As suggested by the name, all microbes are too small to be seen without a microscope. Beyond size, microbes are incredibly diverse. Microbes include bacteria, fungi, and protists. To be able to live harmoniously with all of these microbes, we implement numerous practices to control their growth.

On one hand, there are many harmful microbes we try to avoid. Consider the pathogenic bacteria Listeria monocytogenesand Salmonella entericathatcause foodborne illnesses. We use refrigeration to slow the growth of microbes like these and keep food safe to eat. On the other hand, some microbes perform useful functions and we intentionally cultivate them. For example, bakers use warm temperatures to promote the growth of the yeast Saccharomyces cerevisiaeto make bread dough rise. Some microbes can be both harmful or beneficial in different conditions. For instance, Escherichia coli can cause gastrointestinal illness when ingested but can produce life-saving synthetic insulin in an industrial setting. Understanding the fascinating growth of microbes helps us develop practices to maintain balanced interactions with these microorganisms.

Features of microbes

Microbes are diverse creatures. Many have unique features and capabilities, yet they share a few common characteristics (Figure 2). Most microbes are made of only one or a few cells. Every microbial cell is surrounded by a cell membrane. The membrane controls the movement of material in and out of the cell. This allows the cell to bring in important material, like nutrients, while expelling waste. Some microbes are also surrounded by a cell wall. The wall provides a structure to enclose the internal components of the cell. Within its interior, each cell carries the DNA encoding its genome. Other structures in the cell perform metabolic functions that are essential for life.

Mechanisms of microbial growth

Microbial growth refers to an increase in number of cells rather than an increase in cell size. Many microbes (including Escherichia coli, Salmonella enterica, and Listeria monocytogenes) are unicellular, meaning they are made of only one cell. The size of any unicellular microbe is limited by the capacity for the essential components of the cell to support its survival. For example, the integrity of the cell wall is impaired when cells become too large. The solution to growing despite limits on cell size is for cells to divide or produce new cells from the original cell. Therefore, the population grows although the size of the individual members of the population remains stable.

Most commonly, a single-cellular microbe divides into two identical new cells during one growth cycle (Figure 3a). The original cell, called the parent cell, makes a copy of its DNA and generates enough material to build the membrane, wall, and molecular machines for two cells. The parent cell slightly increases in size to accommodate these additional materials. Then, the parent cell begins to contract at the middle and a new piece of cell wall is assembled at the site of contraction. This process continues until the parent cell is split into two cells with complete cell walls. The resulting cells are called the daughter cells. Because both daughter cells are identical, cell division is also called replication. Replication in this manner leads to a rapid increase in the number of cells as each daughter cell begins the cycle again by acting as a parent cell. Cell division can look slightly different for microbes with different shapes (Figure 3b), but the key principles remain the same.

As long as the conditions are favorable, one cell produces two new cells in a continuous cycle. Every cycle doubles the number of cells in the population. This is known as exponential growth. Depending on the conditions, the division cycle of E. coli can be as short as 20 minutes. This rapid division leads to a rapid increase in the population size (Figure 3c). Eventually, the population is large enough to have an impact we can detect, such as formation of a physical structure. In a research lab, this might be a “colony,” a mound of bacteria on solid growth media. You might notice this as plaque on your teeth. It takes over a million bacteria to form a visible structure, but this can occur in only about eight hours when conditions are optimal for E. coli.

Some microbes produce new cells asymmetrically. In this situation, one parent cell produces a single daughter cell by a process called budding. During budding the parent cell develops a small protrusion known as the bud. The materials necessary to support a new cell are sent into the bud, which eventually splits from the parent cell to form a new daughter cell. The parent cell continues to make buds, but the budded daughter cells do not divide. Buds can remain connected in a chain or separate into individual cells (Figure 4). Saccharomyces cerevisiae, a yeast used to make bread, is a budding yeast.

There are also multicellular microbes, like algae and the fungi that form molds. For these microbes, multiple cells work together to keep the organism alive. Each cell might perform slightly different functions for the organism. When a parent cell divides, each daughter cell begins to perform specific functions based on its surroundings. The entire organism grows as new cells form and take on new functions. This is similar to the way larger organisms, like animals, grow.

Factors affecting microbial growth

Bacteria Chains

All types of microbial growth are heavily impacted by environmental conditions. One of the most critical factors for microbial growth is the availability of nutrients and energy. Microbes need carbohydrates, fats, proteins, metals, and vitamins to survive, just like animals. The process of using nutrients and converting them into cellular material requires energy. Every microbe has unique nutritional requirements depending on the types of molecules it is capable of making for itself. Most microbes are fairly robust, meaning they can find a way to grow in a variety of nutritional conditions. Nonetheless, microbes grow more slowly when nutrients are limited.

Temperature also impacts microbial growth. Most microbes grow optimally within a certain temperature range dictated by the ability of proteins within the cell to function. In general, at low temperatures, microbes grow slower. At higher temperatures, microbes grow more quickly. For instance, pathogens often grow best at normal body temperature, but slowly at cooler temperatures outside the body or when body temperature increases during a fever. Extremely high temperatures usually denature the components required for the cells to survive and are lethal for many microbes. Nonetheless, a few exceptional microbes actually prefer to grow at very high temperatures or very low temperatures. These microbes, known as extremophiles, can grow near hydrothermal vents where the temperature is above boiling or surrounded by solid ice.

Even when nutrients are available and the temperature is right, many other environmental factors can influence the growth of microbes. These include acidity, availability of water, and atmospheric pressure. Each microbe prefers a range of properties for multiple features of the environment. Overall, microbes typically grow best at a specific set of conditions and less well at other conditions (Figure 5). Specific preferences for growth are as diverse as the types of microbes.

Methods of controlling microbial growth

Decades of research have developed the current understanding of microbial growth to establish the principles outlined above. Establishing common principles allows us to target broad groups of microbes, while unique requirements for growth allows us to target specific microbes. This knowledge enables the control of microbial growth that facilitates many of our interactions with microbes today.

Many methods of control seek to eliminate harmful microbes from foods or equipment. For example, high temperature is often used to kill microbes during cooking or through processes like pasteurization. In this way, potentially harmful microbes are broadly eliminated from the food product making it safe to consume and store. Similarly, chemicals in disinfectants can damage or kill microbes broadly on surfaces. Alcohols like ethanol and isopropanol damage the cell membranes. Without this protective structure, microbes cannot control what enters or exits the cell. Subsequently, microbes cannot retain important nutrients and water. Alternatively, hydrogen peroxide damages structures within the cell. As hydrogen peroxide decomposes, it forms molecules known as free radicals that damage proteins and DNA. Meanwhile, we also use soaps to physically remove microbes from surfaces. The chemical properties of soaps and physical force applied when wiping a surface dislodges the microbes.

When microbes cannot be completely eliminated from a material, such as food products that cannot be heated to high temperatures, measures can be taken to mitigate the growth of microbes. Recognizing how temperature impacts growth, supports the importance of refrigeration. As mentioned, cold temperatures slow the growth of microbes, so refrigeration can delay the growth of microbes in these food products. As described above, microbes can replicate as quickly as every 20 minutes leading to visible growth within only a few hours. At a lower temperature, the cells may divide only once every few hours and it will take multiple days to see visible growth.

Alternatively, when we want to take advantage of microbes, we try to optimize the conditions for their growth. This is why yeasted dough is left at a warm temperature to allow the yeast to grow rapidly. If the dough is refrigerated, it takes much longer to rise. Similarly, to use E. coli for insulin production, we provide bacteria with specific nutrients that facilitate growth.

Given the diversity of microbes in the world, it’s clear that there is still so much we don’t know about how they grow. Continuing to better understand microbial growth will help us live safely with the microbes in our community and make use of their unique capabilities.

Molly Sargen is a PhD student in the Biological and Biomedical Sciences Program at Harvard Medical School.

Nick Lue is a PhD student in the Chemical Biology Program at Harvard University.

Cover image: “Bacteria sample inside petri dish for biotechnology study” by IRRI Images is licensed under CC BY-NC-SA 2.0

For More Information:

• Interested in understanding different types of microbes? Try this page.
• Learn more about the structure of bacterial cells here.
• For more details about cell division, see this page.
• For more details about mechanisms of microbial growth, read this article.
• To learn more about chemical disinfectants, check out this information from the CDC.