A balancing act: Keeping your gut healthy

Introduction
​
Recent scientific research has increasingly highlighted the profound role of the gut microbiota in supporting overall health. This diverse community of microorganisms not only aids in digestion but also plays a critical part in regulating immune responses, metabolism, and even neurological functions. Emerging evidence now links imbalances in gut microbiota, known as dysbiosis, to a wide range of diseases, including autoimmune conditions, metabolic disorders, neurological disorders, and certain cancers [1].
​
Despite the growing recognition of dysbiosis as a key factor in disease, public awareness remains limited, and concrete guidelines from government health agencies and medical societies are lacking. As this field of study continues to expand, it raises important questions about how the public might respond to these discoveries and how to address dysbiosis proactively. Preventive medicine could offer promising solutions by focusing on early diagnosis and correction of microbial imbalances. However, without clear guidelines or widespread clinical recommendations, individuals will have to navigate this complex area on their own in the near term [2]. This article explores the implications of these findings and discusses how to harness this knowledge for disease prevention in the face of regulatory uncertainty. Options range widely from simple diet adjustments, to probiotics, and for those already suffering from relevant disease states, the possibility of fecal microbiota transplantations as a therapeutic choice [3].

References
[1] Afzaal M, Saeed F, Shah YA, Hussain M, Rabail R, Socol CT, Hassoun A, Pateiro M, Lorenzo JM, Rusu AV, Aadil RM. Human gut microbiota in health and disease: Unveiling the relationship. Front. Microbiol. 2022; 13;  https://doi.org/10.3389/fmicb.2022.999001
[2] Abeltino A, Hatem D, Serantoni C, Riente A, De Giulio MM, De Spirito M, De Maio F, Maulucci G. Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine. Nutrients. 2024; 16(22):3806. https://doi.org/10.3390/nu16223806
[3] Andary CM. et al. Dissecting mechanisms of fecal microbiota transplantation efficacy in disease. Trends in Molecular Medicine, 2024; 30 (3): 209 – 222. DOI: 10.1016/j.molmed.2023.12.005

Gut dysbiosis is a concern.

The human gut microbiota [1] is a diverse ecosystem of microorganisms that play crucial roles in supporting health. Dysbiosis [2] refers to a state of imbalance in the microbiota, where shifts in the composition or function of microbial communities disrupt normal host-microbe interactions. This imbalance is present in various diseases (list provided below). Commensal bacteria, such as species from the genera Lactobacillus and Bifidobacterium, promote gut health by producing metabolites like short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate (Table 1). SCFAs nourish colonocytes, strengthen the gut barrier, and exert anti-inflammatory effects [3]. Conversely, pathobionts (microorganisms that are typically harmless but can become pathogenic under certain conditions) can degrade the mucin layer that lines and protects the gut epithelium.

The gut mucin layer is a critical barrier that separates gut microbes from the epithelial cells, preventing direct contact that could trigger inflammation [4]. Pathobionts such as Akkermansia muciniphila (in overabundance), Bacteroides fragilis, Escherichia coli, Clostridium difficile, and species of Fusobacterium can degrade mucin glycoproteins, thinning this protective layer. Degradation of this barrier facilitates microbial translocation, allowing bacteria and their metabolites to penetrate the epithelial layer and enter systemic circulation. This triggers immune activation, promoting inflammation and potentially leading to diseases such as inflammatory bowel disease (IBD), colorectal cancer, and metabolic syndrome.

Dysbiosis can result from multiple factors [5], including:

• Antibiotic use: Broad-spectrum antibiotics disrupt the microbiota, often leading to the overgrowth of opportunistic pathogens.
• Dietary changes: A Western diet rich in fats and sugars but low in fiber can reduce SCFA-producing bacteria and favor the proliferation of pathobionts.
• Infections: Pathogenic infections can shift the microbial community structure.
• Stress and lifestyle: Psychological and physical stressors can alter gut motility and microbiota composition.
• Aging: Natural changes in microbial diversity occur with age, often reducing beneficial species [6].

Dysbiosis is potentially reversible through interventions such as:

• Lifestyle changes: Regular exercise, stress management, and adequate sleep contribute to microbial health.
• Dietary modifications: High-fiber diets can promote SCFA production and restore microbial balance.
• Probiotics and prebiotics [7]: Probiotics introduce beneficial bacteria, while prebiotics provide nutrients that support their growth.
• Fecal microbiota transplantation (FMT): FMT has shown success in treating recurrent C. difficile infections by restoring microbial diversity and has potential for application in other diseases [8].

In summary, dysbiosis disrupts the balance between commensal bacteria and pathobionts, compromising the integrity of the gut mucosa and helping disease. By understanding the factors that cause dysbiosis and implementing targeted interventions, the restoration of a healthy microbiota is achievable, offering potential therapeutic benefits for a wide range of diseases.

References
[1] Sommer, F, & Bäckhed, F. The gut microbiota—masters of host development and physiology. Nature Reviews Microbiology. 2013; 11(4), 227–238.  https://doi.org/10.1038/nrmicro2974
[2] Cleveland Clinic: Dysbiosis
[3] Bedu-Ferrari C, Biscarrat P, Pepke F, Vati S, Chaudemanche C, Castelli F, Chollet C, Rué O, Hennequet-Antier C, Langella P, Cherbuy C. In-depth characterization of a selection of gut commensal bacteria reveals their functional capacities to metabolize dietary carbohydrates with prebiotic potential. mSystems 2024; 9: e01401-23. https://doi.org/10.1128/msystems.01401-23.
[4] Yamaguchi, M, Yamamoto, K. Mucin glycans and their degradation by gut microbiota. Glycoconj. J. 2023; 40, 493–512. https://doi.org/10.1007/s10719-023-10124-9
[5] Healthline: What causes dysbiosis and how is it treated?
[6] Ravikrishnan, A., Wijaya, I., Png, E. et al. Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes. Nat. Commun. 2024; 15, 7751. https://doi.org/10.1038/s41467-024-52097-9
[7] Bermúdez-Humarán, L.G., Chassaing, B. & Langella, P. Exploring the interaction and impact of probiotic and commensal bacteria on vitamins, minerals, and short chain fatty acids metabolism. Microb. Cell Fact. 2024; 23, 172. https://doi.org/10.1186/s12934-024-02449-3
[8] Cleveland Clinic: Fecal Transplant

Comprehensive List of Conditions Strongly Linked to Dysbiosis [1,2]

• Rheumatoid Arthritis (RA)

• Inflammatory Bowel Disease (IBD)
• Irritable Bowel Syndrome (IBS)
• Type 1 Diabetes
• Obesity
• Colorectal Cancer
• Small Intestinal Bacterial Overgrowth (SIBO)
• Cardiovascular Diseases
• Neurological Disorders (including Alzheimer's Disease [3,4] and Parkinson's Disease [5,6])
• Chronic Fatigue Syndrome
• Metabolic Syndrome
• Asthma and Allergies
• Autism Spectrum Disorder (ASD)
• Chronic Liver Disease

____________________________________________________________
References:
[1] Cleveland Clinic: Dysbiosis
[2] WebMD: What is dysbiosis
[3] Thakkar, A, Vora, A, Kaur, G et al. Dysbiosis and Alzheimer’s disease: role of probiotics, prebiotics and synbiotics. Naunyn-Schmiedeberg's Arch. Pharmacol. 2023; 396, 2911–2923. https://doi.org/10.1007/s00210-023-02554-x
[4] Oral Dysbiosis and Alzheimer’s Disease Risk
 [5] Medical News Today: Study in humans confirms link between Parkinson's and gut bacteria imbalance.
[6] Munoz-Pinto MF, Candeias E, Melo-Marques I et al. Gut-first Parkinson’s disease is encoded by gut dysbiome. Mol. Neurodegeneration. 2024; 19, 78. https://doi.org/10.1186/s13024-024-00766-0

---

Table 1. Selected Short Chain Fatty Acid (SCFA) producing bacterial specie

Genus	Species
Lactobacillus	johnsonii
	acidophilus
	gasseri
	casei
	paracasei
	rhamnosus
	salivarus
	fermentum
	plabtarum
Bifidobacterium	bifidum
	longum
	breve
	adolescentis
	animalis
Faecalibacrerium	prautnizii
Roseburia	inulinivorans
Anaerobutyricum	halii
Bacteroides	xylanisplvens

 

---

Table 2. Selected mucin degrading bacterial specie

Family	Genus	Species
Akkermansiaceae	Akkermansia	muciniphilia
Bacteroidaceae	Bacteroides	Fragilis
Enterobacteriaceae	Escherichia	Many species from the Enterobacteriaceae family
	Klebsiella
	Proteus
	Salmonella
	Shigella
	Yersinia
Enterococcaceae	Bavariicoccus	Many species from the Enterococcaceae family
	Catellicoccus
	Enterococcus
	Melossococcus
	Pilibacter
	Tetragenococcus
	Vagococcus
Peptococcaceae	Peptococcus	Many species from the Peptococcaceae family
	Peptostreptococcus
	Ruminococcus
Peptostreptococcaceae	Clostridiodes	Difficile (syn. Clostridium difficile)
Clostridiaceae	Clostridium	disporicum
		tertium
	Paraclostridium	benzoeliticum
Oscillospriraceae	Anaerotruncus	colihominis
Erysipelotrichaceae	Holdemania	filiformis
		massilliensis
Eggerthellaceae	Eggerthella	Lenta and others
Fusobacteriaceae	Fusobacterium	Many species from the Fusobacterium genus

 

---

Diagnosis

In clinical practice, symptoms of gastrointestinal disturbances often guide the diagnosis of gut dysbiosis. Your healthcare providers could apply tests that are traditionally used to investigate potential gut microbiota imbalances. These include:

Breath tests: These tests can help diagnose conditions like small intestinal bacterial overgrowth (SIBO) [1] and carbohydrate malabsorption. Patients showing chronic digestive problems, abdominal pain, bloating, frequent passing of gas, constipation, and diarrhea, are good candidates for these tests. Hydrogen and methane production are measured after consuming a particular test sugar — usually lactose, fructose, sucrose, sorbitol, glucose, or lactulose, depending on the condition your healthcare provider is checking for [2].

Biomarker-Based Testing: For example, testing for zonulin, a protein that regulates the permeability of the tight junctions between epithelial cells in the gut lining. Elevated levels in stool or blood may be a result of increased intestinal permeability, often associated with dysbiosis. Alternatively, testing for short chain fatty acids (SCFA) levels like butyrate and propionate in stools or blood, can signal reduced beneficial microbial activity.

Stool analysis: Stool analysis could be undertaken at various levels of complexities. A focused approach consists simply of cultures to find specific pathogens or overgrowth of bacteria such as Clostridium difficile or Escherichia coli. More comprehensively, your healthcare providers could order molecular testing based on either 16S Ribosomal RNA sequencing to obtain a detailed view of microbial composition and diversity, or alternatively next generation sequencing to identify all microbial DNA in the sample, including bacteria, viruses, fungi, and archaea, offering a broader analysis compared to 16S sequencing [3,4]. At the next higher level is Comprehensive Stool Analysis (CSA), which in addition to profiling gut microbiota, will also address digestive markers (elastase, fat and protein malabsorption), inflammatory markers (calprotectin and lactoferrin), metabolic markers ( pH and beta-glucuronidase), intestinal barrier function (zonulin as discussed previously, and secretory IgA) and SCFA [5-7].

All the above aside, patients who have no obvious gastrointestinal disturbances, but preliminary symptoms of diseases linked to dysbiosis, face a difficult choice. A comparable situation exists for those without any symptoms but are known to be predisposed through family history and genetics. In the absence of conclusive cause and effect evidence, the medical profession and government health agencies stay silent about the need for evaluating the status of their gut microbiota and how to remedy any imbalances. All decisions rest with the patients and healthcare providers. On the other hand, medical literature abounds with pro and con opinions arguing either way [8]. Patients who are initiative-taking can always reach out to direct-to-consumer companies in the burgeoning gut microbiome industry [9,10]. Hopefully, they will do so with expert help from properly licensed genetic counselors [11] and healthcare providers. We will next discuss options for supporting or improving gut microbiota balance.

References
[1] Small Intestinal Bacterial Overgrowth. [Updated 2023 Apr 17]. Sorathia SJ, Chippa V, Rivas JM. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK546634/
[2] WebMD: What To Know About Hydrogen Breath Tests
[3] Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Allaband C et al. Clinical Gastroenterology and Hepatology. 2019; 17 (2), 218 – 230. DOI: 10.1016/j.cgh.2018.09.017
[4] Clinician Guide to Microbiome Testing. Staley C, Kaiser T & Khoruts A. Dig. Dis. Sci. 2018; 63, 3167–3177. https://doi.org/10.1007/s10620-018-5299-6
[5] Genova Diagnostics: GI Effects
[6] Doctor’s Data: Comprehensive Stool Analysis
[7] Diagnostic Solutions Laboratory: GI-MAP
[8] Dr. Ruscio DC: Should You Use a Stool Test to Check Your Gut Health?
[9] Rupa Health: Revolutionizing Gut Health: The Rise of Microbiome Testing Companies and Their Impact on Personalized Medicine. Scott Bingman. October 28, 2024.
[10] Microbiome Therapeutics Innovation Group (MTIG)
[11] National Society of Genetic Counselors: Find a genetic counselor  

Lifestyle interventions

Irrespective of a diagnosis of dysbiosis you could always care for your gut microbiota by reviewing three elements of lifestyle that are known to affect gut health: exercise, sleep, and stress management.

Exercise and Gut Microbiota: Studies have shown that physical activity enhances microbial diversity, which is a marker of a healthy gut [1]. Regular exercise increases the abundance of beneficial bacteria, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Bacteroides and Roseburia, all of which are associated with anti-inflammatory effects and gut barrier integrity. Mechanistically, exercise-induced increases in butyrate-producing bacteria contribute to the production of short-chain fatty acids (SCFAs), compounds that provide energy to colonocytes and strengthen the gut barrier. Studies in both humans and animals have shown that sedentary lifestyles correlate with reduced microbial diversity, while active individuals show greater microbial richness and resilience to dysbiosis [2]. The Center for Disease Control (CDC) recommendation for adult physical activity is 150 minutes of moderate-intensity activity per week, or 75 minutes of vigorous-intensive activity, or an equivalent combination of both [3].

Sleep and Gut Health: Sleep plays a crucial role in supporting gut health [4]. Research has shown that adequate sleep helps support the integrity of the gut barrier, which prevents the entry of harmful substances and pathogens [5]. A study conducted by Shandong University found that specific gut bacteria, such as Lachnospiraceae UCG004 and Odoribacter, are associated with longer sleep duration and better sleep quality. These bacteria promote a healthy gut environment, which in turn supports better sleep [6]. Conversely, poor sleep can lead to gut dysbiosis, increasing the risk of various health issues. The minimum sleep requirement for adults (18 years or older) is 7 hours or more per day according to the Sleep Foundation [7].

Stress Management and Gut Microbiota: Chronic stress negatively affects gut health through the gut-brain axis. Stress can alter gut motility, reduce mucus secretion, and increase intestinal permeability, creating an environment conducive to dysbiosis. Elevated cortisol levels, a hallmark of stress, have been linked to shifts in microbial composition, with reductions in beneficial species like Lactobacillus and Bifidobacterium [8]. Stress management techniques, including mindfulness meditation, yoga, and deep-breathing exercises, can mitigate these effects by modulating the hypothalamic-pituitary-adrenal (HPA) axis and reducing systemic inflammation [9]. Such interventions have been shown to restore microbial diversity and improve gut health. General guidelines for finding and resolving stress are provided by the CDC [10].

In summary, regular exercise, adequate sleep, and stress management represent simple yet effective strategies to support gut health and combat dysbiosis. By fostering microbial diversity, promoting beneficial species, and reducing systemic inflammation, these lifestyle interventions empower individuals to actively contribute to their own gut health. Incorporating these habits into daily life not only improves microbial balance but also offers broader health benefits that extend beyond the gut. For a full review of lifestyle factors potentially affecting your health, please consult the Lifestyle section of this website.

References
[1] Clarke SF, Murphy EF, O'Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 ; 63 :1913-1920. https://doi.org/10.1136/gutjnl-2013-306541
[2] Khaledi, M, Darvishi, M, Sameni, F et al. Association between exercise and changes in gut microbiota profile: a review. Sport Sci. Health. 2024; 20: 273–286. https://doi.org/10.1007/s11332-023-01132-1
[3] What Counts as Physical Activity for Adults
[4] Kado, DM. Night-to-night sleep duration variability and gut microbial diversity: more evidence for a brain-gut microbiome-sleep connection. Sleep. 2024; 47(3), zsae005, https://doi.org/10.1093/sleep/zsae005
[5] Smith RP, Easson C, Lyle SM, Kapoor R, Donnelly CP, Davidson EJ, Parikh E, Lopez JV, Tartar JL. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One. 2019;14(10): e0222394. doi: 10.1371/journal.pone.0222394. PMID: 31589627; PMCID: PMC6779243.
[6] Yue M, Jin C, Jiang X, Xue X, Wu N, Li Z, Zhang L. Causal Effects of Gut Microbiota on Sleep-Related Phenotypes: A Two-Sample Mendelian Randomization Study. Clocks Sleep. 2023; 5(3):566-580. doi: 10.3390/clockssleep5030037. PMID: 37754355; PMCID: PMC10527580.
[7] How much sleep do you need. Eric Suni & Abhinav Singh. Updated May 13, 2024.
[8] Almand, AT, Anderson, AP, Hitt, BD et al. The influence of perceived stress on the human microbiome. BMC Res. Notes. 2022; 15: 193. https://doi.org/10.1186/s13104-022-06066-4
[9] Chrousos, G. Stress and disorders of the stress system. Nat. Rev. Endocrinol. 2009; 5: 374–381. https://doi.org/10.1038/nrendo.2009.106
[10] CDC: Stress management

Dietary modifications

Diet plays a critical role in shaping the gut microbiota, and targeted dietary changes can help restore balance in patients diagnosed with dysbiosis. Corrective action involves identifying deficiencies or imbalances in the diet and implementing modifications to promote beneficial microbial growth while minimizing harmful influences.

Diet deficiencies identification: Professional guidance from a registered dietician [1,2] can provide a comprehensive and tailored approach to understanding dietary influences on dysbiosis. A dietitian can perform a thorough dietary assessment, often using tools like food frequency questionnaires (FFQs) or dietary recall. This helps find deficiencies in fiber, essential nutrients, or overconsumption of inflammatory foods. Patients without access to professional help can take initiatives like self-tracking. Using food diaries or apps (e.g., MyFitnessPal, Lifesum, Cronometer and MyNetDiary) can help monitor dietary patterns and identify trends, such as low fiber intake or excessive processed foods. If symptoms like bloating or irregular bowel movements are present, correlating them with dietary habits could help find triggers. Following evidence-based dietary recommendations, such as increasing whole foods and reducing processed foods, can be a good starting point.

Corrective Dietary Actions: Studies have shown that high-fiber diets increase microbial diversity and SCFA production, both critical for supporting gut health [3]. So, fiber is the cornerstone of a gut-friendly diet as it serves as a substrate for beneficial bacteria to produce short-chain fatty acids (SCFAs). Increasing dietary proportion of fruits, vegetables, legumes, whole grains, and prebiotic-rich food like garlic, onions, bananas, and asparagus are particularly beneficial. In contrast, diets high in refined sugars and low in fiber are linked to reduced microbial diversity and inflammation [4]. Excessive sugar and processed food consumption can promote the growth of pathogenic bacteria and contribute to dysbiosis. The best course of action is to replace sugary snacks with healthier options like nuts or seeds and minimize ultra-processed foods.

High intake of saturated fats can disrupt gut microbiota, while omega-3 fatty acids have been shown to increase microbial diversity and promote the growth of beneficial anti-inflammatory bacteria [5]. Saturated fats should be replaced with healthier options like fatty fish (salmon, mackerel), flaxseeds, and walnuts. Another key point to remember in a healthy diet is the effect of alcohol. Excessive alcohol intake disrupts gut microbial composition, and it is essential to reduce consumption to the recommended level or simply cut it completely from your diet [6]. Finally, the effect of hydration also requires consideration since it supports healthy digestion. Although the CDC does not have specific recommendations for daily water intake, the need of the vast majority is 3.7 L for men and 2.7 L for women, from all sources, with variations allowed for unusual circumstances like strenuous exercises, dehydration, and body habits [7,8].

Lifestyle changes and diet modifications may not be sufficient for certain conditions, intervention with probiotics is the next choice level, which we will consider below.

References
[1] Search for a dietician.
[2] Find a nutrition expert.
[3] The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Makki, Kassem et al.. Cell Host & Microbe.2018; 23(6), 705 – 715. https://doi.org/10.1016/j.chom.2018.05.012
[4] Singh, R.K., Chang, HW., Yan, D. et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 2017; 15, 73. https://doi.org/10.1186/s12967-017-1175-y
[5] Watson H, Mitra S, Croden FC, et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2018; 67:1974-1983. https://doi.org/10.1136/gutjnl-2017-314968
[6] CDC: About moderate alcohol use.
[7] Michael N. Sawka, Samuel N. Cheuvront, Robert Carter, Human Water Needs, Nutrition Reviews. 2005; 63, Issue suppl_1, S30–S39, https://doi.org/10.1111/j.1753-4887.2005.tb00152.x
[8] MedicalNews Today: How much water should you drink a day?

Probiotics

Probiotics, live microorganisms that confer health benefits when consumed in adequate amounts, are a promising intervention for patients with dysbiosis. When lifestyle changes and dietary modifications prove insufficient, probiotics can help restore microbial balance [1]. However, patients face a range of choices: probiotics from fermented foods and as dietary supplements. Each option has unique benefits and considerations, often requiring medical supervision to ensure safety and efficacy.

Probiotics from Fermented Foods: Fermented foods such as yogurt, kefir, sauerkraut, kimchi, and miso naturally have probiotics [2]. These foods are rich in beneficial bacteria like Lactobacillus and Bifidobacterium, which can help restore gut balance [3]. The advantage of consuming probiotics through fermented foods is that they are part of a natural diet and can be easily incorporated into daily meals. However, the concentration of probiotics can vary, and not all fermented foods have the same strains or amounts of beneficial bacteria [2].

Probiotics as Dietary Supplements: Probiotic supplements are another choice, available in various forms such as capsules, tablets, and powders. These supplements have specific strains of bacteria like Lactobacillus rhamnosus GG, Bifidobacterium breve, or Saccharomyces boulardii, tailored to address health issues (e.g., relief of diarrhea, improved immunity). The advantage of supplements is the ability to choose products with known concentrations of probiotics and specific strains that have been studied for their health benefits [4]. However, the quality and efficacy of probiotic supplements can vary, and as dietary supplements they are not regulated by the FDA in the same way as medications [5]. It is essential to select reputable brands and consult with a healthcare provider to ensure the chosen supplement is proper for the patient's needs [6]. The need for consultation with a healthcare provider will be even more acute for patients who use the services of direct-to-consumers microbiome companies (see the microbiome profiling section of this website). In addition to the results of gut microbiota and gut health, these companies will often suggest a host of dietary supplements including pre- and probiotics as remedies. The amount of information and choices could be overwhelming to some.

Live Biotherapeutic Products (LBP): It is important to note that the FDA has recently created this new therapeutic entity defined as “ biological product that: i) contains live organisms, such as bacteria; ii) is applicable to the prevention, treatment, or cure of a disease or condition of human beings; and iii) is not a vaccine”. LBPs must undergo rigorous clinical trials and be approved before marketing. Probiotics could be defined as LBPs to treat specific diseases. To date no probiotic has been approved as LBPs.

References
[1] Cleveland Clinic: Probiotics
[2] Veryell Health: 20 Probiotic Foods With Good Bacteria. Amber J. Tresca. Published September 22, 2023
[3] WebMD: Top Foods High in Probiotics
[4] Sanders, ME, Merenstein, DJ, Reid, G et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat. Rev. Gastroenterol. Hepatol. 2019; 16, 605–616. https://doi.org/10.1038/s41575-019-0173-3
[5] Doron S, Snydman DR. Risk and Safety of Probiotics, Clinical Infectious Diseases. 2015; 60, Issue suppl_2, S129–S134, https://doi.org/10.1093/cid/civ085
[6] Clinical Guide to Probiotic Products Available in USA

Prebiotics and Synbiotics

While often mentioned together with probiotics, these terms describe distinct, yet complementary interventions aimed at supporting gut health.
Prebiotics are non-digestible food components, primarily fibers and oligosaccharides, which promote the growth and activity of beneficial gut bacteria. Unlike probiotics, which are live microorganisms, prebiotics serve as "food" for these bacteria. Common prebiotic substances include inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS). Found in foods like garlic, onions, bananas, and whole grains, prebiotics selectively nourish beneficial bacteria such as Bifidobacteria and Lactobacilli, fostering an environment that discourages the growth of harmful microbes.

Synbiotics are products that combine prebiotics and probiotics in a synergistic way to enhance their overall effectiveness. The prebiotics in synbiotic formulations support the survival and activity of the included probiotic strains, ensuring that they reach the gut in sufficient numbers and thrive. For example, a synbiotic product might pair a strain of Bifidobacterium with its preferred prebiotic, such as FOS. This combination can amplify the health benefits, improving gut health, boosting immune function, and even supporting metabolic processes.
Prebiotics and synbiotics are often used alongside probiotics to maximize their potential benefits. For instance, adding prebiotic-rich foods or supplements to a probiotic regimen can create a more hospitable environment for the beneficial microbes, improving their efficacy. Similarly, synbiotics can streamline this process by providing both components in a specific product.
​
Together, these interventions address various health goals, from improving digestion and reducing inflammation to supporting immune health and preventing certain diseases. Their targeted use is increasingly recognized as a vital strategy for enhancing the microbiome and achieving better health outcomes.
Finally, patients who are already suffering from diseases with a strong microbiome association, the ultimate choice for correcting dysbiosis is Fecal Microbiota Transplantation which we will consider below.

Fecal Microbiota Transplantation: A Therapeutic Option for Microbiome-Linked Diseases

Fecal microbiota transplantation (FMT) is an innovative medical procedure in which processed stool from a healthy donor is introduced into a recipient's gastrointestinal tract to restore a balanced gut microbiota. This approach targets dysbiosis implicated in various diseases, as either a contributing factor or a potential cause [1]. FMT has garnered attention for its effectiveness in treating certain conditions and its potential to revolutionize microbiome-centered therapies.

FMT has achieved the greatest success in treating recurrent Clostridioides difficile infection (CDI), a condition characterized by severe diarrhea and inflammation resulting from disrupted gut microbiota, often due to antibiotic use. Studies report cure rates exceeding 85% in patients who failed traditional therapies such as antibiotics like vancomycin or metronidazole. Emerging evidence suggests FMT may also help patients with other microbiome-associated diseases [2]:

Inflammatory Bowel Disease (IBD): In conditions like ulcerative colitis (UC) and Crohn’s disease, FMT has shown potential to induce remission or improve symptoms, though results are inconsistent and depend on factors like donor selection and disease severity.
Irritable Bowel Syndrome (IBS): Some studies show symptom relief and improved quality of life following FMT in patients with IBS.

Metabolic Disorders: Research exploring FMT for obesity, insulin resistance, and metabolic syndrome shows promise but requires more evidence.

Neurological Conditions: Preliminary studies have investigated FMT’s role in autism spectrum disorders and Parkinson’s disease, hypothesizing that gut-brain axis modulation may offer therapeutic benefits.

FMT offers three advantages including the restoration of microbial diversity. It directly reintroduces a diverse microbiome, overcoming the limitations of probiotics or dietary interventions that may not sufficiently alter the gut ecosystem. It has proven more effective than antibiotics for recurrent CDI, reducing relapse rates and potentially lowering healthcare costs. Unlike antibiotics, FMT does not exert selective pressure on pathogens, reducing the risk of developing antimicrobial resistance.

On the other hand, FMT is still a subject of regulatory and safety concerns [3]. Despite its success, FMT is not universally standardized. While safe, FMT can cause mild to moderate transient adverse effects such as abdominal discomfort, fever, and bacteremia. Risks include transmission of undetected pathogens or adverse immune responses, needing stringent donor screening and oversight [4]. FMT effectiveness can depend on factors like donor microbiome composition, disease type, and recipient characteristics, which are not fully understood [5]. While FMT has shown short-term efficacy, long-term outcomes, and potential risks, such as the development of other conditions, remain unclear.

Traditional therapies, such as antibiotics for CDI or immunosuppressants for IBD, aim to manage symptoms or reduce inflammation but do not address the underlying microbial imbalance. FMT offers a unique approach by directly targeting dysbiosis. However, it is more invasive and currently lacks the robust evidence base and standardization that traditional therapies have. Additionally, its role as a frontline therapy is still limited, often being reserved for cases refractory to standard treatments.

Resources for patients and healthcare providers who wish to access FMT as a therapeutic modality include the following:

FDA-approved formulations of Fecal Microbiota Transplantation (FMT): Two formulations (Rebyota and Vowst) were approved for prescription to treat recurrence of Clostridioides difficile infection (CDI) in patients 18 years and older who have completed antibiotic treatment for recurrent CDI [6,7].

OpenBiome is a non-profit stool bank that provides investigational FMT preparations to registered physicians treating patients with recurrent Clostridioides difficile infection (CDI). They offer a "Find a doctor" tool on their website to help patients locate healthcare providers who can perform FMT.

The American Gastroenterological Association (AGA) provides guidelines and resources for FMT, including information on indications, donor screening, and procedural aspects [8].

Patients and doctors can also explore ongoing clinical trials related to FMT through databases like ClinicalTrials.gov, which provide information on eligibility criteria and study locations.

Besides helping patients and healthcare providers navigate the process of accessing FMT and they also ensure that it is used safely and effectively.

In summary, FMT is an innovative approach in treating dysbiosis-related diseases, offering a targeted and effective solution for conditions like recurrent CDI and holding promise for broader applications. While its advantages, particularly in restoring microbiome diversity, are clear, the challenges of safety, regulation, and variable outcomes must be addressed through rigorous research and standardization. As our understanding of the microbiome grows, FMT may evolve from a niche intervention to a cornerstone of personalized medicine.

References
[1] Karimi M, Shirsalimi N, Hashempour Z, Salehi OH, Sedighi E, Beigi F, Mortezazadeh M. Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review. Frontiers in Immunology. 2024, 15.  https://doi.org/10.3389/fimmu.2024.1439176
[2] Goldenberg, D, Melmed, GY. Fecal Transplant: The Benefits and Harms of Fecal Microbiota Transplantation. 2023; In: Pimentel M, Mathur R, Barlow GM (eds) Clinical Understanding of the Human Gut Microbiome. Springer, Cham. https://doi.org/10.1007/978-3-031-46712-7_9
[3] AAMC News: The potential and pitfalls of fecal transplants
[4] Goloshchapov OV, Olekhnovich EI, Sidorenko SV et al. Long-term impact of fecal transplantation in healthy volunteers. BMC Microbiol. 2019; 19, 312. https://doi.org/10.1186/s12866-019-1689-y
[5] Lee JY, Kim Y, Kim J et al. Fecal Microbiota Transplantation: Indications, Methods, and Challenges. J Microbiol. 2024. https://doi.org/10.1007/s12275-024-00184-3
[6] AGA: FDA approves first FMT therapy and issues guidance, December 2, 2022
[7] Vowst® (Seres Therapeutics)
[8] AGA Clinical Practice Guideline on Fecal Microbiota–Based Therapies for Select Gastrointestinal Diseases. Peery AF. et al. Gastroenterology. 2024; 166 (3): 409 – 434. https://doi.org/10.1053/j.gastro.2024.01.008