Targeting the Human Microbiome With Antibiotics, Probiotics, and Prebiotics: Gastroenterology Enters the Metagenomics Era
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The Metagenomics Era and Gastroenterology
The science of metagenomics and the international Human Microbiome Project1, 2 has ushered in a new era for the field of gastroenterology. Microbes and their genetic content outnumber their mammalian counterparts by 1–2 orders of magnitude,3 and the spatial topography of these populations within the gut shows a nonrandom distribution that ultimately benefits both microbe and host.4 New ribosomal RNA- and whole genome-based technologies have highlighted the potential importance of novel
Lessons From Antibiotics
The suppression and elimination of microbial pathogens by antibiotics represents a time-tested approach in medical management. However, recent studies have highlighted the profound changes in microbial populations that result from applications of antimicrobial agents. Molecular profiling of infant fecal microbial communities after antibiotic treatment showed drastic reductions in total bacterial densities and alterations in population composition.28 These changes of the human-associated
Lessons from Probiotics
The concept of probiotics, a term that literally means “for life,” was introduced at the turn of the 20th century. Russian Nobel laureate Elie Metchnikoff, in his 1907 opus The Prolongation of Life: Optimistic Studies, proposed the heretical idea that ingesting microbes could have beneficial effects for human beings, especially to treat digestive diseases.50 Nearly a century later, British microbiologist Roy Fuller suggested that the beneficial effects are mediated by an improvement in
Lessons From Prebiotics and Synbiotics
The term prebiotic was first introduced by Gibson and Roberfroid in 1995 and is defined as “a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.”81 Prebiotics are typically oligosaccharides or more complex saccharides that are selectively used by commensal bacteria, including species considered to be beneficial for the human host. Prebiotics
Acute Gastroenteritis
Although specific microbial pathogens have been identified as causative agents of acute gastroenteritis, antibiotic treatment strategies are limited in scope and can exacerbate toxin-mediated diseases in this context. One successful antibiotics-based strategy includes rifaximin for the prevention and treatment of traveler's diarrhea.88 In contrast to antibiotics, microbial supplementation by probiotics has been studied as an approach for prevention or attenuation of acute gastroenteritis.
Antibiotic-Associated Diarrhea and Colitis
Antibiotic-induced alterations of the gastrointestinal microbiota clearly increase the risk of antibiotic-associated gastrointestinal disorders in susceptible individuals. Intuitively, the concomitant addition of beneficial microbes to treatment regimens for these disorders offers new opportunities to promote microbial diversity and resilience of the host. A series of systematic reviews showed promising but incomplete evidence to recommend probiotic preparations to treat C. difficile–associated
Inflammatory Bowel Disease
Microbial dysbiosis has been implicated in inflammatory bowel disease (IBD),103 and numerous studies have documented differences in gastrointestinal microbial populations between healthy individuals and patients with IBD. In the IL-10–deficient mouse model of colitis, replacement of missing lactobacilli populations ameliorated cecal inflammation.104, 105, 106, 107 A recent review of probiotic therapies for the induction and maintenance of remission in IBD concluded that beneficial effects were
Irritable Bowel Syndrome and Related Disorders
Irritable bowel syndrome (IBS) has been characterized as constipation-predominant, diarrhea-predominant, or as a disorder with alternating patterns of constipation or diarrhea predominance. IBS includes a constellation of symptoms such as abdominal pain, bloating, and altered defecation patterns. Microbial manipulation could provide tangible benefits for intestinal fermentation or gas production, intestinal motility patterns, and antinociceptive or anti-inflammatory effects that result from
Necrotizing Enterocolitis
Considering the wide fluctuations observed in intestinal microbial populations during infancy and the profound effects of antibiotic treatment in neonates, it is important to carefully consider the selection of microbiological therapeutics for patients with necrotizing enterocolitis (NEC). Despite the lack of any specific microbial cause for NEC and the significant questions that remain about the efficacy of antimicrobial strategies for this disorder, agents such as ampicillin plus cefotaxime
Future Perspectives: What Lies Ahead?
As the global efforts in human microbiome-related research and therapeutic microbiology expand,154 the knowledge base of the diversity present in the gastrointestinal tract and the functional consequences of that diversity will be more deeply appreciated. Careful selection of drugs, nutrients, and bacterial strains is essential because antibiotics, probiotics, and prebiotics have a variety of biological effects, each with implications for the human microbiome. Careful preclinical screens,
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Conflicts of interest The authors disclose the following: Dr. Versalovic has received unrestricted research support from Biogaia AB, Stockholm, Sweden, and has received honoraria from Group Danone, Paris, France.
Funding This work was supported by National Institutes of Health (NIH) National Institute of Digestive and Kidney Disease (R01 DK065075 and P30 DK56338), NIH National Center for Complementary and Alternative Medicine (R01 AT004326 and R21 AT003482), and the US Department of Defense (HR0011-08-1-0009).