The normal flora or microbial population of a particular site of the body consists of a unique community of core and secondary microbiota that evolved through a symbiotic relationship with the host and a competitive relationship with other species. The host provides a place to colonize, nutrients, and some protection from unwanted species (innate immune responses). The microbes provide needed metabolic functions, stimulate innate and regulatory immunity, and prevent colonization with unwanted pathogens (Fig. 1). The ability to tolerate the amount of oxygen or lack thereof (redox state) and the pH and salt concentration, as well as to scavenge essential minerals and harvest and metabolize the available nutrients, deter mines the numbers and nature of the species that populate a site of the body. Anaerobic or facultative anaerobic bacteria colonize most of the sites of the body because of the lack of oxygen in sites such as the mouth, intestine, and genitourinary tract.
Fig1. Intestinal microbiota protection against enteric infections. (I) Saturation of colonization sites and consumption of nutrients limit pathogen access to host tissues; (II) the microbiota prime innate immunity by stimulating mucin production, immunoglobulin (Ig)A, and antimicrobial peptides (AMPs); and (III) the microbiota stimulate interleukin (IL)-22 expression, which increases epithelial resistance, and IL-1β production, which promotes recruitment of inflammatory cells. (From Khosravi, A., Mazmanian, S., 2013. Disruption of the gut microbiome as a risk factor for microbial infections. Curr. Opin. Microbiol. 16, 221–227.)
The composition of the microbiota is influenced by per sonal hygiene (e.g., use of soap, deodorants, mouthwash, skin peels, enemas, vaginal douches), diet, water source, medicines (especially antibiotics), and exposure to environ mental toxins. Drinking well water versus chlorinated city water or a diet consisting of fiber, sugar, or fats can select for different intestinal bacteria based on their ability to use the essential minerals (e.g., iron) and nutrients. Alteration of the environment with foods or medicines can also alter the microbiota (Fig. 2). These changes can be acceptable if the core microbiome and critical functional properties of the microbiome are maintained but can result in disease if these functions are lost. Historically, the greatest concern with the use of broad-spectrum antibiotics was the selection of resistant bacteria; however, a greater concern should be the disruption of the microbiome and loss of essential functions. Because antibiotics are not completely selective for the targeted pathogen, the use of antibiotics is always associated with some degree of toxicity.
Fig2. Effect of antibiotics on the gut microbiota. Fecal samples were collected from four patients treated with antibiotics: patient A, moxifloxacin; patient B, penicillin + clindamycin; patient C, cefazolin followed by ampicillin/sulbactam; and patient D, amoxicillin. Fecal samples collected before, dur ing (e.g., 3_D is day 3 of therapy), and after therapy were used to assess the total microbiota. Changes are noted both during therapy and after therapy is discontinued. (A) Total microbiota (16 S rRNA gene). (B) Metabolically active microbiota (16 S rRNA transcripts). (From Perez-Cobas, A.E., Artacho, A., Knecht, H., et al., 2013. Differential effects of antibiotic therapy on the structure and function of human gut microbiota. PLoS One 8, e80201.)
Of the more than 150 species of bacteria that colonize the gut of a healthy adult individual, most are members of Bacteroidetes (e.g., Bacteroides) and Firmicutes (e.g., Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus), with Actinobacteria (e.g., Bifidobacterium) present in smaller numbers. Interestingly, the importance of many of these bacteria was not appreciated before gene sequencing was used to identify and quantitate the gut microbiota. Within the colon, some bacteria establish their niche by waging interspecies warfare with bacteriocins (e.g., colicins produced by Escherichia coli), other antibacterial proteins, and metabolites that deter other species from growing. These molecules also benefit the host by eliminating invading bacteria including Salmonella, Shigella, Clostridioides difficile, Bacillus cereus, and other pathogens. The bacteria must also resist antimicrobial peptides and immunoglobulin (Ig) A produced by the host and released into the bowel.
Metabolism of nutrients plays a major role in the symbiotic relationship between the human host and microbe. Bacteria in the human gut are responsible for metabolizing complex carbohydrates (including cellulose) to provide small-chain fatty acids such as acetate, propionate, and butyrate that can be readily transported and used by the cells of our body. These acids also limit the growth of undesirable bacteria. Other bacteria graze on the carbohydrates, the mucins that line the epithelium, or the oils released in our sweat. Bacteroidetes and Firmicutes are more efficient than others at breaking down complex carbohydrates, including plant cell wall compounds (cellulose, pectin, and xylan) and host-derived carbohydrates, including those attached to the mucins or chondroitin sulfates of the protective mucous layer of the intestine. Increases in the ratio of these bacteria in the gut microbiome can lead to a higher efficiency in the storage of the metabolic by-products. This can be a benefit for malnourished populations or patients with debilitating diseases such as cancer or can lead to obesity in well-nourished populations.
