Microbiome therapies
Gut microbiome therapy aims to restore the age-related microbial diversity associated with optimum health, with the microbiome as a target of treatment or as a source of biotherapeutics. Its experimental forms include prebiotics, probiotics, postbiotics, strategies that target enterosynes, and phage therapy.
Aims of therapy
Strong associations between alterations of the gut microbiome (dysbiosis) and diseases have led scientists to develop therapies that target a malfunctioning gut. The purpose of gut microbiome therapy is to restore the appropriate age-related microbial diversity associated with optimum health (eubiosis). The gut microbiome can be a target of treatment, or it can serve as a source of biotherapeutics.
Research now focuses on the microbiota or their associated metabolites as potential therapies. The treatment options explored include prebiotics, probiotics, postbiotics, synbiotics, faecal microbiota transplants and live biotherapeutic products. Experimental microbiome therapies need large-scale clinical studies to verify their impact on human health.
Microbial signatures as biomarkers
Microbial signatures could serve as personalised biomarkers to distinguish a healthy individual from someone with a disease. Yet treating diseases on the basis of this belief has had limited success, which does not diminish the value and importance of the gut microbiome. As clinical biomarkers, microbial signatures associated with symptoms can indicate the effectiveness of personalised treatment, for example in COVID-19 or neurovascular disease.
The microbiota and drug action
Researchers are looking into ways to modulate the impact of therapies by manipulating the gut microbiota. The heterogeneous gut microbiota can change the potency and subsequent actions of drugs by binding them and altering their conformation, metabolising them, modifying liver or mucosal barrier function, or regulating gene expression.
Prebiotics
Prebiotics are fermented, nondigestible food ingredients that host microbes use selectively and that provide health benefits by enhancing the growth of one or more bacteria in the colon. They regulate enzymes that modulate xenobiotics, inhibit pathogen growth and modulate immune responses. Prebiotics can be applied directly to the skin and vagina or taken orally to reach the intestines. Although preliminary studies reveal positive effects of prebiotics in depression, colorectal cancer, schizophrenia, anxiety and stress, large randomised controlled studies are required to confirm them.
Probiotics
Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit to the host". Most probiotics are bacteria and yeasts, and they are commonly found as ingredients in fermented products such as yogurt, cheese and fermented soy.
Among their many effects, probiotics can prevent colonisation by pathogenic bacteria, improve gut microbiome diversity, regulate the immune system and prevent allergies. Beneficial effects of probiotics have been observed in diabetes, depression, cancer, ulcerative colitis, autoimmune arthritis, multiple sclerosis and rotavirus diarrhoea. In premature infants, probiotics modify gut microbiome diversity in a way that appears to improve host immunity and to reduce feeding intolerance and mortality. The use of probiotics is still experimental, and large-scale studies are required to confirm their positive impact as treatment.
The efficacy of probiotics depends on the stage of the disease when the probiotic is given, the dose, dietary modifications suited to the requirements of the introduced probiotic, the overall health of recipients and the duration of treatment. In a personalised approach to treatment, identifying the microbial signature of the gut will influence the selection and efficacy of the appropriate probiotic.
Most probiotics are considered safe as food supplements, although patients who are immunocompromised should not use them. The FDA considers live biotherapeutic products, which are probiotics used to treat specific diseases, to be drugs that require stringent regulation before they can be sold.
Postbiotics
Postbiotics are "a preparation of inanimate microorganisms and/or their components that confer a health benefit to the host". They are nontoxic, found in high concentrations, ubiquitous in the human body and stable when introduced into the circulatory system, and they can be given through multiple routes.
Examples of prebiotics, probiotics and postbiotics
| Therapy | Sources | Examples |
|---|---|---|
| Prebiotics | Vegetables (broccoli, onions, asparagus, garlic), bananas, chicory root, grains (wheat), fruits, nuts, or purified dietary supplements | Psyllium, oligosaccharides and fructooligosaccharides, human milk oligosaccharides, lactosucrose, xylooligosaccharides, polyphenols, galactooligosaccharide, mannan oligosaccharide, resistant starch, polyunsaturated fatty acids, arabinooligosaccharides, dietary fibres |
| Probiotics | Fermented foods such as kefir and yogurt; nasal sprays or oral supplements | Lactobacillus rhamnosus, L. helveticus, L. casei, L. acidophilus, Streptococcus thermophilus, Lactococcus lactis, Enterococcus faecalis, L. bulgaricus, L. paracasei, L. plantarum, Bifidobacterium longum, B. bifidum, Bacillus coagulans, Faecalibacterium prausnitzii, Akkermansia muciniphila, Lactobacillus reuteri, L. brevis, B. breve, Bacteroides fragilis, L. gasseri |
| Postbiotics | Nonviable microbial cells or cell fragments | Cell byproducts (short-chain fatty acids), trimethylamine oxide (TMAO), cell components (such as proteins and endo- and exopolysaccharides), enzymes, microbe-targeted toxins, bile acids, acetic acid, tryptophan, lactic acid, vitamins, peptidoglycans |
Enterosynes
Enterosynes are diverse molecules that function as bioactive lipids or peptides, microbiota, hormones, immune molecules and nutrients. Strategies that target enterosynes could potentially treat diseases such as type 2 diabetes.
Phage therapy
Phages are viruses that infect bacteria, and phage cocktails have been found to be safe for patients. In a recent study, a combination of five phages had an immunosuppressive effect on patients with IBD, and in a phase 1 human clinical trial phages suppressed Klebsiella pneumoniae, a common pathogenic bacterial strain in IBD. Faecal virome transplantation studies have been deferred because of controversies over the safety of phages as therapeutic agents. Large randomised controlled studies are needed to confirm the impact of these new biomolecular therapies.