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Bacterial Botox: Microbiome-Based Interventions for Timeless Health

microbiome based interventions

In the past three articles of our microbiome series, we have taken you on a journey to explore the fascinating world of the human gut microbiome. We have seen how these microscopic organisms, which inhabit every nook and cranny of our bodies, contribute to our general health, interact with various organ systems, and even influence the aging process. As we embark on a new chapter, we will dig into the innovative realm of gut-microbiome-based interventions that greatly promise to improve general health and promote healthy aging.


This article is part four of a four-part series on the microbiome and longevity.

  1. From the Gut Up: The Latest Breakthroughs in Microbiome Research
  2. Gut Feelings: The Surprising Links Between Gut and Your Body’s Vital Organs
  3. The Clockwork of Microbiome-Based Aging: Tracing the Lifelong Impact of the Gut Microbiome
  4. Bacterial Botox: Microbiome-Based Interventions for Timeless Health

We have explored the myriad factors impacting the gut ecosystem’s dynamics daily, indicating that various methods are available for modulating the gut microbiome. These approaches can be employed therapeutically or prophylactically, depending on their application, objectives, and modes of action. Some techniques focus on altering the entire microbial community, while others zero in on particular taxa or strains.

This article explores six different approaches to modulating the gut microbiome:

  1. Diet
  2. Prebiotics
  3. Probiotics
  4. Synbiotics & Postbiotics 
  5. Fecal Microbiota Transplantation
  6. Phage Therapy and Fecal Filtrate Transplantation

1. Diet

The Impact of Diet on Gut Microbiota

For example, it is well-documented that the highly refined components in processed foods, pervasive in Western diets, undergo facile absorption within the small intestine. This process fosters bacterial proliferation and engenders an unfavorable microbial composition, which correlates with metabolic profiles that negatively impact immune functions. Moreover, the emulsifiers found in processed foods, such as carboxymethylcellulose, have been demonstrated to exacerbate chronic intestinal inflammation in murine models by enhancing the ability of adherent-invasive Escherichia coli (E. coli) to attach and move along the surface of intestinal epithelial cells. Concurrently, the elevated fat content encourages the proliferation of pathobionts, which have been implicated in an array of detrimental outcomes, including inflammation, compromised intestinal barrier function (“leaky gut”), glucose dysregulation, and hepatic steatosis (Natividad et al., 2018; Valdes et al., 2018; Zinöcker & Lindseth, 2018). 

Contrasting Effects of Processed Foods and Whole Plant-Based Foods

In stark contrast, whole plant-based foods—including vegetables, fruits, legumes, whole grains, and nuts—constitute the primary source of natural dietary fibers. These fermentable fibers are transformed into metabolites such as short-chain fatty acids (SCFAs), which are pivotal in maintaining the equilibrium between pro-inflammatory and anti-inflammatory mechanisms. Furthermore, fiber-rich diets foster the development of a robust intestinal mucus layer and barrier, effectively reducing the susceptibility to pathogenic infection (Desai et al., 2016). Human intervention studies have highlighted the inhibitory influence of vegetable and fruit consumption on the growth of pathogenic clostridia (e.g., Clostridium perfringens and Clostridium histolyticum), among other beneficial effects on the microbiome (Cui et al., 2019).

Undoubtedly, we have all heard about the adverse effects of processed foods and the advantageous properties of whole foods. Yet, what evidence-based dietary pattern most benefits the gut microbiome remains an open question, which we shall address right now.   

The Influence of the Ketogenic Diet on Gut Microbiome

The ketogenic diet emphasizes limited carbohydrate consumption while incorporating high fat and sufficient protein intake. The keto diet attracted the attention of microbiome researchers after being correlated with a decreased frequency of seizures in children suffering from therapy-resistant epilepsy through increases in Akkermansia and Parabacteroides that ultimately modulates hippocampal GABA/glutamate ratios (Lindefeldt et al., 2019). However, reductions in health-promoting bacteria such as Bifidobacteria and Eubacterium rectale and their metabolites were observed in individuals under ketogenic diets, without pre-existing conditions (Russell et al., 2011). This suggests that keto diets may have a less positive influence on gut and overall health in disease-free individuals. Therefore, while existing research underscores the short-term benefits of ketogenic diets for specific population groups, the long-term implications of fermentable fiber restriction and high-fat content may adversely impact gut microbiome composition and immune response in healthy subjects.

Comparing High-Fiber vs. High-Fermented Food Diets

In a meticulously conducted investigation, Stanford University researchers compared two trendy dietary patterns renowned for their gut health benefits: high-fiber and high-fermented food diets. For a duration of 10 weeks, participants assigned to the high-fiber diet were encouraged to incorporate legumes, seeds, whole grains, nuts, vegetables, and fruits into their meals. Meanwhile, those in the high-fermented food group increased their consumption of yogurt, kefir, fermented cottage cheese, kimchi, and other fermented vegetables, vegetable brine drinks, and kombucha tea. Both cohorts aimed to respectively augment their baseline consumption by at least 20 grams of fiber per day and 6 servings of fermented foods daily.

Intriguingly, the researchers discovered that a 10-week increase in fiber intake alone was insufficient to enhance microbiota diversity and elicit immune responses in a consistent manner. In contrast, in the same time window, a fermented food diet successfully increased microbiome diversity and decreased inflammation markers across all participants (Wastyk et al., 2021). 

These findings further corroborate evidence suggesting that vegetarian/vegan diets, replete with fibers, phytonutrients, and antioxidants, can potentially confer gut health benefits (Tomova et al., 2019). However, a vegetarian diet may not be universally suitable, as it may prove challenging to acquire adequate quantities of specific nutrients such as vitamin B12, iron, omega-3 fatty acids and more. Moreover, the vegetarian diet is not inherently guaranteed to restrict the consumption of processed foods, refined sugars, and unhealthy fats, which would be necessary for maintaining a healthy microbiome.

The Mediterranean Diet and its Benefits for Gut Health

While a universally optimal diet for gut health remains elusive, owing to the variability in individual needs and responses to food, the Mediterranean diet has been recognized for its pronounced benefits on the gut microbiome (Nagpal et al., 2019). 

Characterized by a well-balanced composition, the Mediterranean diet emphasizes a high intake of plant-based foods, moderate poultry, fish, and olive oil consumption, and a limited intake of dairy products and red meat. This dietary pattern has been inversely correlated with a reduced risk of dementia, cancer, and cardiovascular disease, as well as an enrichment of anti-inflammatory bacteria, such as Akkermansia versus Fusobacterium (Illescas et al., 2021; Renzella, 2018; Shannon et al., 2023). Moreover, a high level of adherence to the Mediterranean diet has been linked to increased fecal SCFAs. 

In contrast, low adherence is associated with elevated urinary trimethylamine N-oxide (TMAO) levels—known to be connected to atherosclerosis and cardiovascular disease (De Filippis et al., 2016). Thus, the Mediterranean diet is a compelling candidate for promoting gut health and overall well-being. 

Even in the context of healthy aging, a one-year-long intervention study has illustrated the capacity of the Mediterranean diet to enhance health status and mitigate frailty via the gut microbiome in elderly individuals aged 65 to 79. The authors observed that the abundance of bacteria enriched by adherence to the Mediterranean diet was negatively correlated with inflammatory markers, such as C-reactive protein while exhibiting positive associations with several markers of reduced frailty and improved cognitive function (Ghosh et al., 2020). These findings suggest that the Mediterranean diet may be an efficacious approach for bolstering gut health and attenuating the risk of age-related conditions.

Fasting Practices and their Effects on Gut Microbiome

While the significance of dietary intake during non-fasting periods is paramount, certain fasting practices may contribute to an enhanced diversity of the gut microbiome and increased levels of specific gut bacteria. 

Existing evidence indicates that intermittent fasting could potentially bolster both the gut microbiome and the host’s overall health. Studies conducted on young men during the Islamic holy month of Ramadan, which involved fasting for approximately 16 hours daily, revealed elevated levels of Lachnospiraceae in the participants’ gut microbiomes. These beneficial bacteria are associated with reduced risks of cancer and inflammatory bowel disease and improved cardiovascular and mental health. Unfortunately, the composition of the microbiome reverted to baseline levels upon the cessation of intermittent fasting (Su et al., 2021). 

In a similar vein, a study involving both male and female participants demonstrated that fasting for 16 hours daily resulted in decreased body weight, improved blood lipid profiles, increased bacterial diversity, and a shift in favor of anti-inflammatory Lactobacillus and Bifidobacterium over pathogenic bacteria (Khan et al., 2022). 

A Synergistic Approach for Optimal Gut Health

In relation to dietary recommendations, we advocate for individuals to embrace a well-balanced Mediterranean diet or NOVOS Longevity Diet enriched with 6 daily servings of fermented food and partake in a 16/8 intermittent fasting routine (confining caloric intake to an 8-hour window). This synergistic approach will foster a vibrant and balanced environment for your gut. 

The NOVOS Longevity Diet builds upon the foundations of the Mediterranean diet and incorporates the latest research findings to make modifications that further optimize its potential impact on healthspan and lifespan. 

2. Prebiotics

What Are Prebiotics?

As officially defined, prebiotics are ‘substrates selectively utilized by host microorganisms that confer health advantages’ (Davani-Davari et al., 2019). While current prebiotic definitions have faced criticism for failing to differentiate between prebiotic dietary fibers and non-prebiotic ones, non-digestible carbohydrates (NDCs) are widely acknowledged for their capacity to influence the gut microbiome’s composition and functionality. As the name suggests, NDCs are a category of fibers that remain undigested in the small intestine, subsequently providing sustenance for gut bacteria in the colon. These NDCs can be derived from natural sources or synthesized through chemical processes, exhibiting notable physicochemical and physiological properties.

Prominent examples of prebiotic NDCs include lactulose, β-glucans, inulin, mannooligosaccharides (MOS), fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS), pecticoligosaccharides (POS), and transgalactosylated oligosaccharides (TOS). The microbial inhabitants of the colon possess the ability to thrive on these NDCs and ferment them into SCFAs, which are crucial for stimulating mucus production, maintaining intestinal barrier integrity, and safeguarding against inflammation. Distinct microbial species are necessary for breaking down specific fiber types, with certain bacteria being highly specialized and contributing substantially to fiber degradation. The more complex the fiber structure, the more specialized the bacterial response becomes.

Efficacy of Prebiotics in Addressing Cardiovascular Health and Diabetes

In support of prebiotics’ efficacy, the consumption of β-glucans enriched food, namely whole oats, has been demonstrated to lower both systolic and diastolic blood pressure (Reynolds et al., 2022), thereby benefiting individuals afflicted with cardiovascular disease (CVD) and hypertension, two primary causes of mortality in the United States. In a similar vein, the daily intake of 60 grams of β-glucans enriched whole-grain barley and/or brown rice, has been associated with an augmentation of microbial diversity and a reduction in peak postprandial glucose levels (Martínez et al., 2013), which is a characteristic marker of diabetes.

Prebiotics and Healthy Aging

Concerning using prebiotics for healthy aging, numerous studies have investigated the effects of prebiotic supplementation in older individuals. For example, the utilization of FOS and inulin has been shown to increase the abundance of Bifidobacteria, subsequently leading to a reduction in inflammatory markers and an increase in stool frequency (Bouhnik et al., 2004; Kleessen et al., 1997). Likewise, the consumption of GOS has been found to significantly elevate Bifidobacteria levels and enhance the production of the bacterial fermentation by-product butyrate (Toward et al., 2012). These results suggest that prebiotic interventions could potentially counteract the observed decline in bifidobacterial populations with age. 

Furthermore, to evaluate the health outcomes linked to enhanced microbiome composition, numerous studies have showcased the effectiveness of prebiotics in combating common age-related pathological conditions found in older adults. For example, two frailty criteria were improved following the administration of combined inulin and FOS mixture in the elderly (Buigues et al., 2016). Similarly, intake of 5-10 g/d of prebiotics (including oligofructose-enriched inulin, GOS, and β-glucans)has been consistently associated with improved behavior and brain functions (Serra et al., 2019). Although more trials are needed to validate the efficacy of prebiotics in enhancing healthspan, the results underscore their potential in promoting a healthier microbiome composition and consequently improving age-related health outcomes.

3. Probiotics

What Are Probiotics?

Probiotics, defined as “living microorganisms that confer health benefits upon the host when ingested in sufficient quantities,” may be obtained through fermented foods or supplementary formulations (Hill et al., 2014). However, it is crucial to note that not all fermented foods can be classified as probiotics. Fermentation is characterized by the growth of desirable microorganisms and enzymatic alterations of food constituents, yet living microbes at the time of consumption are not obligatory for a food item to be deemed fermented. 

Examples of fermented foods that do not necessarily qualify as probiotics include sourdough bread and beer, as these products undergo additional processing, such as baking or filtration, which can eliminate the living microorganisms. Furthermore, certain fermented foodstuffs, such as kimchi and kombucha, have yet to be scientifically verified as probiotics, as research has not conclusively demonstrated that the microorganisms present in these items are directly responsible for specific health advantages.

Fermented Foods and Gut Microbiome Diversity

After having set the record straight on the definition of probiotics, we can now delve into the scientific underpinnings of these beneficial microorganisms starting with food formulation. 

A 17-week randomized, prospective investigation involving an increased intake of fermented foods revealed that these consistently enhanced gut microbiome diversity while simultaneously reducing blood-based inflammatory markers (Wastyk et al., 2021). 

A contemporary review expounded upon the advantages of fermented food consumption for healthy aging, attributing the benefits to the enrichment of health-promoting components. Notably, Lactic Acid bacteria and Bifidobacteria, which are instrumental in the fermentation of yogurt, play a vital role in generating bioactive compounds that confer antihypertensive, antioxidant, antidiabetic, and antiallergic properties to the base ingredient (Melini et al., 2019). Fascinatingly, an association has been observed between yogurt consumption and an increased relative abundance of species used as yogurt starters (Streptococcus thermophilus and Bifidobacterium animalis subsp. lactis) in individuals who also exhibited improved metabolic health, as evidenced by reduced visceral fat (Le Roy et al., 2022). Similarly, fermented grain-based products, which undergo fermentation by various yeasts, bacteria, and fungi, possess health-promoting components that exhibit antioxidant, antihypertensive, antidiabetic, and FODMAP-reducing properties.

Probiotic Supplements and Aging

On the other hand, probiotic supplements exhibit a wide spectrum of intricacy, ranging from single strains to elaborate microbial consortia consisting of multiple strains derived from diverse species. Within the context of aging, studies have discovered that specific probiotics, including Lactobacillus and Bifidobacterium, can mitigate immunosenescence and bolster the efficacy of influenza vaccinations in elderly individuals (Rowland, 2022). 

Moreover, a systematic evaluation of randomized controlled trials determined that supplementation with probiotics, such as Bacillus coagulans, Fecalibacterium prautznitzi, and various Lactobacillus and Bifidobacterium strains, appears to be effective in modulating gut microbiota composition in healthy older adults, with moderate impacts on immune function. 

Nonetheless, the influence of probiotic supplementation on other health outcomes, including cognitive function and lipid biomarkers, remains uncertain, underscoring the necessity for further well-structured, adequately powered investigations to elucidate whether and how probiotics contribute to healthy aging (Hutchinson et al., 2021). 

Next-Generation Probiotics and Akkermansia muciniphila

Interestingly, progress in sequencing technology has deeply enhanced our understanding of the relationships between various species and strains of microorganisms and their implications for health conditions. We can now develop previously unattainable probiotics by capitalizing on sequencing data to pinpoint strains that may prove advantageous for specific ailments. Such probiotics selected through this methodology are called ‘next-generation probiotics’ (NGPs) (O’Toole et al., 2017).

Among the most extensively researched NGPs is Akkermansia muciniphila, which has been inversely associated with several human diseases (Zhang et al., 2019). Despite the safety of live A. muciniphila administration being verified, only its inactive pasteurized form (postbiotic) was proven to improve fat mass, insulin sensitivity, and cholesterol levels in overweight/obese volunteers (more on this later) (Depommier et al., 2019). Before live A. muciniphila can become a widely utilized NGP, it is crucial to collect further results from large-scale clinical trials. 

Scientists recently conducted a study to discover new factors that contribute to healthy aging. Using a method called causal Mendelian randomization, the researchers discovered that a specific type of Lactobacillus bacteria has a significant impact on increasing the chances of living longer in humans (Liu et al., 2023). However, further human trials are necessary to confirm the potential of these probiotics in extending the period of good health.

4. Synbiotics & Postbiotics 

What Are Synbiotics & Postbiotics?

The International Scientific Association for Probiotics and Prebiotics (ISAPP) has recently elucidated the definitions of microbiome-related terminology, encompassing synbiotics and postbiotics. Synbiotics are defined as a “mixture consisting of live microorganisms (probiotics) and substrates (prebiotics) that are selectively employed by host microorganisms, thereby conferring a health advantage to the host.” In contrast, postbiotics denote a “composition of inanimate microorganisms and/or their constituents, which imparts a health benefit to the host” (Swanson et al., 2020).

The Health Benefits of Synbiotics

It is crucial to clarify that the term ‘synbiotic,’ is not necessarily intended to imply synergy or the enhancement of combined effects. Rather, it denotes the concept of ‘together.’ 

A plethora of randomized controlled trials (RCTs), predominantly involving adults suffering from metabolic disorders, have been conducted to scrutinize the health benefits of purported synbiotics. In these studies, the most frequently employed live microorganisms within the tested formulations are species from the Lactobacillus, Bifidobacterium, and Streptococcus genera. The substrate constituents typically consist of GOS, inulin, or FOS, although dosages can fluctuate considerably, ranging from a mere 100 mg to a more substantial 10–15 g per day (Swanson et al., 2020).

Postbiotics and Inanimate Strains

At the opposite end of the spectrum, numerous extant postbiotics incorporate inanimate strains from recognized probiotic taxa within certain genera of the Lactobacillaceae family or the Bifidobacterium genus (Andresen et al., 2020; Cicenia et al., 2014). 

One example of an intact cellular postbiotic is the utilization of pasteurized A. muciniphila cells. A study revealed that the pasteurized cells of A. muciniphila, as opposed to the living ones, enhanced insulin sensitivity, and decreased plasma cholesterol levels, thanks to the function of a membrane protein (Depommier et al., 2019). A similar case, p40, has been recognized as the constituent responsible for the advantageous effects of the common probiotic Lactobacillus Rhamnosus GG (LGG). It is plausible that this protein may impact the gut’s ecology, as the administration of LGG significantly elevated the richness and evenness of the microbiome when given during the first week of life (Shen et al., 2018). 

Bacterial Metabolites as Postbiotics

Concerning bacterial metabolites as postbiotics, short chain fatty acids in dosages ranging from 150mg to 300mg per day have demonstrated beneficial modifications to the adult gut microbiome (Banasiewicz et al., 2020). Similarly, secondary bile acids such as ursodeoxycholic acid (UDCA) and its conjugated form, tauroursodeoxycholic acid (TUDCA), have been associated with positive effects on gut health (Lu et al., 2021). As the field of postbiotics continues to advance, understanding the interplay between these inanimate microorganisms, metabolites, and end products will be crucial in developing effective therapies to promote overall well-being.

Gerobiotics for Longevity Research

In the realm of longevity research, the term ‘gerobiotics’ has been introduced to delineate probiotic strains and their derived postbiotics, which possess the capacity to beneficially mitigate the fundamental mechanisms of aging, diminish physiological aging processes, and consequently extend the host’s health span (Tsai et al., 2021). Many probiotics boasting anti-aging potential have been identified, primarily employing invertebrate organism models for examining lifespan extension and rodent models for investigating intricate molecular mechanisms. Clinical trials for select probiotic strains belonging to the species of Lactobacillus casei, Bifidobacterium lactis, and Lactobacillus plantarum, have been successfully completed. Encouraging outcomes pertaining to their anti-aging effects have been discovered, including enhancements in immune and cognitive functions (Dong et al., 2013; Hwang et al., 2019; Miller et al., 2017).

5. Fecal Microbiota Transplantation 

What Is Fecal Microbiota Transplantation (FMT)?

Fecal Microbiota Transplantation (FMT) involves the transfer of fecal matter from a healthy donor to an afflicted patient to ameliorate or cure specific medical conditions. Contemporary interest in FMT was piqued by its efficacious application in treating Clostridium difficile infections (van Nood et al., 2013). Consequently, it has garnered approval from the Food and Drug Administration (FDA) as a treatment for such infections. Various methods of FMT delivery are employed, including capsules, colonoscopies, nasoenteric tubes, and enemas. The most efficacious transplantation technique has been lower gastrointestinal endoscopy (96.4%), whereas enema administration has proven the least effective (50.2%). 

Determinants of FMT Success

FMT has been observed to induce substantial alterations in the recipient’s microbiome ecology, encompassing the introduction of previously absent species or strains. Initial investigations implied that the donor’s microbiome composition was the primary determinant of FMT success, giving rise to the notion of ‘super donors’—individuals possessing a highly diverse microbiome that proved most beneficial for FMT. However, this concept has faced criticism due to the absence of consistent experimental substantiation. Instead, donor-recipient compatibility appears to be a critical element in forecasting and augmenting FMT success. As such, the recipient’s microbiome may also play a vital role, with a diminished recipient microbiome offering the greatest likelihood of engraftment (Podlesny et al., 2022; Schmidt et al., 2022).

Autologous FMT (aFMT)

In an effort to obviate the reliance on external donors, autologous FMT (aFMT) has been investigated. aFMT entails patients receiving their own stool, which is preserved prior to undergoing treatment, as opposed to fecal matter from distinct donors. For example, aFMT has demonstrated effectiveness in facilitating the recovery of a patient’s microbiome after antibiotic treatment (Taur et al., 2018). In a metabolic study, by utilizing samples procured following the completion of a Mediterranean dietary intervention and subsequently administered over a 6-month period, aFMT has been found to bolster weight loss maintenance and glycemic control as conferred by the diet (Rinott et al., 2021). 

Potential of FMT in Extending Longevity

Several compelling preclinical studies have highlighted the potential of FMT to extend longevity in laboratory animals. In one such study, fecal microbiota transplantation from wild-type mice was found to enhance both healthspan and lifespan in progeroid mouse models (Bárcena et al., 2019). 

Correspondingly, another research group revealed that age-associated hallmarks, including central nervous system (CNS) inflammation, retinal inflammation, the loss of critical functional proteins in the eye, and increased intestinal barrier permeability, could be reversed in aged mice through the transfer of young donor microbiota (Parker et al., 2022). 

Furthermore, additional investigations have shown that fecal transplantation of microbiome from young donors reversed aging-associated differences in neuroimmunity (Boehme et al., 2021), as well as in physical fitness and skin hydration (Kim et al., 2022). 

Therapeutic Benefits of FMT in Metabolic and Neurodegenerative Diseases

Despite the paucity of concrete evidence supporting fecal microbiota transplantation’s (FMT) role in enhancing human longevity, preliminary investigations have illuminated its potential therapeutic benefits in combating metabolic and neurodegenerative diseases, thereby promoting healthy aging. For example, FMT originating from a lean donor has demonstrated a favorable impact on the microbial composition in obese recipients, as evidenced by the increase of butyrate-producing bacteria and enhanced insulin sensitivity six weeks post-procedure (Udayappan et al., 2014). In a similar vein, recent studies on Parkinson’s disease patients documented the transient amelioration of motor and non-motor symptoms following three FMT sessions, including a sustained improvement in constipation (Segal et al., 2021).

While these findings offer a tantalizing glimpse into the potential of FMT as a viable treatment for age-related disorders and longevity, it is crucial to acknowledge their preliminary nature. Further human trials are imperative to substantiate the efficacy of FMT in these contexts.

6. Phage Therapy and Fecal Filtrate Transplantation

What Is Phage Therapy and Fecal Filtrate Transplantation (FFT)?

Phage therapy and fecal filtrate transplantation (FTT) represent two innovative approaches designed to manipulate the gut microbiome, ultimately bestowing health advantages upon the host. Although neither method has been rigorously examined within preclinical or clinical models pertaining to age-related disorders, both interventions harbor considerable therapeutic promise within the realm of microbiome-based treatments.

Phage Therapy: Targeting Specific Bacteria

Phage therapy encompasses the use of bacteriophages that specifically target bacteria. Various phage cocktails have been formulated to address Clostridium difficile and Klebsiella pneumoniae overgrowth (Federici et al., 2022; Nale et al., 2018). While the safety of these mixtures has been corroborated through human studies, instances of phage resistance have been documented within gut bacterial species, potentially correlating with heightened inflammation in the gastrointestinal tract (Lourenço et al., 2020). Additionally, certain phage treatments have been found to exert unintended consequences on non-target species. Consequently, these side effects can alter the gut’s metabolome, thereby influencing the bioavailability of molecules in the host (Gogokhia et al., 2019). Further research is needed to thoroughly comprehend the direct and indirect ramifications of phage therapy on both the microbial community and host.

The Promising Potential of Fecal Filtrate Transplantation (FFT) in Microbiome Manipulation

Fecal filtrate transplantation (FFT) remains in its nascent stages of development. As a response to the absence of standardization in fecal microbiota transplantation (FMT), fecal filtrates endeavor to eliminate microbial cells while preserving the viral components and minuscule molecules present in donor samples, thereby promoting alterations in the recipient’s microbiome. Preliminary findings indicate a 27% enhancement in the efficacy of FFT treatment of Clostridium difficile infections compared to FMT (Ott et al., 2017). Nevertheless, comprehensive comparisons between FMT and FFT must be conducted to draw definitive conclusions.

Exploring New Frontiers: Microbiome-Based Approaches for Age-Related Disorders

The potential of microbiome-based interventions in promoting longevity and healthy aging is a captivating area of exploration. Novel approaches such as fecal microbiota transplantation, NGPs, phage therapy, and fecal filtrate transplantation provide a glimpse into the untapped therapeutic possibilities for combating age-related disorders. As our understanding of the complex microbial communities within our bodies continues to evolve, future research will undoubtedly reveal new insights and applications. 

As we conclude our in-depth exploration of the microbiome, it is clear that our understanding of these complex microbial communities is ever-evolving. We hope this series has provided you, our esteemed reader, with an evidence-based and holistic view of the microbiome, inspiring you to appreciate the intricate interplay between these microscopic organisms and our overall well-being.

Together, let us eagerly anticipate the advancements that lie ahead.


Maria Corlianò, Ph.D.

Dr. Maria Corlianò is an Italian biologist with 8 years of experience in biomedical research at top-ranked laboratories across Europe and Asia. At the age of 23, she was awarded the Singapore International Graduate Award by A*STAR/National University of Singapore, a merit-based Ph.D. scholarship investing in young aspiring scientific talents. During this time, she investigated the role of the gut microbiome in human health and disease, leading to groundbreaking results in the field, as showcased by her publications and her presence at international conferences. 

Dr. Maria Corlianò is now the Co-founder and CTO of OSbiome, an AI-driven precision recommendation platform that helps people improve their lives through the gut microbiome.


References

  1. Andresen, V., Gschossmann, J., & Layer, P. (2020). Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: A multicentre, randomised, double-blind, placebo-controlled clinical trial. The Lancet Gastroenterology & Hepatology, 5(7), 658–666. https://doi.org/10.1016/S2468-1253(20)30056-X
  2. Banasiewicz, T., Domagalska, D., Borycka-Kiciak, K., & Rydzewska, G. (2020). Determination of butyric acid dosage based on clinical and experimental studies – a literature review. Gastroenterology Review, 15(2), 119–125. https://doi.org/10.5114/pg.2020.95556
  3. Bárcena, C., Valdés-Mas, R., Mayoral, P., Garabaya, C., Durand, S., Rodríguez, F., Fernández-García, M. T., Salazar, N., Nogacka, A. M., Garatachea, N., Bossut, N., Aprahamian, F., Lucia, A., Kroemer, G., Freije, J. M. P., Quirós, P. M., & López-Otín, C. (2019). Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nature Medicine, 25(8), 1234–1242. https://doi.org/10.1038/s41591-019-0504-5
  4. Boehme, M., Guzzetta, K. E., Bastiaanssen, T. F. S., van de Wouw, M., Moloney, G. M., Gual-Grau, A., Spichak, S., Olavarría-Ramírez, L., Fitzgerald, P., Morillas, E., Ritz, N. L., Jaggar, M., Cowan, C. S. M., Crispie, F., Donoso, F., Halitzki, E., Neto, M. C., Sichetti, M., Golubeva, A. V., … Cryan, J. F. (2021). Microbiota from young mice counteracts selective age-associated behavioral deficits. Nature Aging, 1(8), 666–676. https://doi.org/10.1038/s43587-021-00093-9
  5. Bouhnik, Y., Raskine, L., Simoneau, G., Vicaut, E., Neut, C., Flourié, B., Brouns, F., & Bornet, F. R. (2004). The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: A double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study. The American Journal of Clinical Nutrition, 80(6), 1658–1664. https://doi.org/10.1093/ajcn/80.6.1658
  6. Buigues, C., Fernández-Garrido, J., Pruimboom, L., Hoogland, A., Navarro-Martínez, R., Martínez-Martínez, M., Verdejo, Y., Mascarós, M., Peris, C., & Cauli, O. (2016). Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial. International Journal of Molecular Sciences, 17(6), 932. https://doi.org/10.3390/ijms17060932
  7. Cicenia, A., Scirocco, A., Carabotti, M., Pallotta, L., Marignani, M., & Severi, C. (2014). Postbiotic Activities of Lactobacilli-derived Factors. Journal of Clinical Gastroenterology, 48(Supplement 1), S18–S22. https://doi.org/10.1097/MCG.0000000000000231
  8. Cui, J., Lian, Y., Zhao, C., Du, H., Han, Y., Gao, W., Xiao, H., & Zheng, J. (2019). Dietary Fibers from Fruits and Vegetables and Their Health Benefits via Modulation of Gut Microbiota. Comprehensive Reviews in Food Science and Food Safety, 18(5), 1514–1532. https://doi.org/10.1111/1541-4337.12489
  9. Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S., Berenjian, A., & Ghasemi, Y. (2019). Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods, 8(3), 92. https://doi.org/10.3390/foods8030092
  10. De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., Lazzi, C., Turroni, S., Cocolin, L., Brigidi, P., Neviani, E., Gobbetti, M., O’Toole, P. W., & Ercolini, D. (2016). High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut, 65(11), 1812–1821. https://doi.org/10.1136/gutjnl-2015-309957
  11. Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., Falony, G., Raes, J., Maiter, D., Delzenne, N. M., de Barsy, M., Loumaye, A., Hermans, M. P., Thissen, J.-P., de Vos, W. M., & Cani, P. D. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study. Nature Medicine, 25(7), 1096–1103. https://doi.org/10.1038/s41591-019-0495-2
  12. Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., Pudlo, N. A., Kitamoto, S., Terrapon, N., Muller, A., Young, V. B., Henrissat, B., Wilmes, P., Stappenbeck, T. S., Núñez, G., & Martens, E. C. (2016). A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, 167(5), 1339-1353.e21. https://doi.org/10.1016/j.cell.2016.10.043
  13. Dong, H., Rowland, I., Thomas, L. V., & Yaqoob, P. (2013). Immunomodulatory effects of a probiotic drink containing Lactobacillus casei Shirota in healthy older volunteers. European Journal of Nutrition, 52(8), 1853–1863. https://doi.org/10.1007/s00394-012-0487-1
  14. Federici, S., Kredo-Russo, S., Valdés-Mas, R., Kviatcovsky, D., Weinstock, E., Matiuhin, Y., Silberberg, Y., Atarashi, K., Furuichi, M., Oka, A., Liu, B., Fibelman, M., Weiner, I. N., Khabra, E., Cullin, N., Ben-Yishai, N., Inbar, D., Ben-David, H., Nicenboim, J., … Elinav, E. (2022). Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell, 185(16), 2879-2898.e24. https://doi.org/10.1016/j.cell.2022.07.003
  15. Ghosh, T. S., Rampelli, S., Jeffery, I. B., Santoro, A., Neto, M., Capri, M., Giampieri, E., Jennings, A., Candela, M., Turroni, S., Zoetendal, E. G., Hermes, G. D. A., Elodie, C., Meunier, N., Brugere, C. M., Pujos-Guillot, E., Berendsen, A. M., De Groot, L. C. P. G. M., Feskins, E. J. M., … O’Toole, P. W. (2020). Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: The NU-AGE 1-year dietary intervention across five European countries. Gut, 69(7), 1218–1228. https://doi.org/10.1136/gutjnl-2019-319654
  16. Gogokhia, L., Buhrke, K., Bell, R., Hoffman, B., Brown, D. G., Hanke-Gogokhia, C., Ajami, N. J., Wong, M. C., Ghazaryan, A., Valentine, J. F., Porter, N., Martens, E., O’Connell, R., Jacob, V., Scherl, E., Crawford, C., Stephens, W. Z., Casjens, S. R., Longman, R. S., & Round, J. L. (2019). Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis. Cell Host & Microbe, 25(2), 285-299.e8. https://doi.org/10.1016/j.chom.2019.01.008
  17. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Canani, R. B., Flint, H. J., Salminen, S., Calder, P. C., & Sanders, M. E. (2014). The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506–514. https://doi.org/10.1038/nrgastro.2014.66
  18. Hutchinson, A. N., Bergh, C., Kruger, K., Sűsserová, M., Allen, J., Améen, S., & Tingö, L. (2021). The Effect of Probiotics on Health Outcomes in the Elderly: A Systematic Review of Randomized, Placebo-Controlled Studies. Microorganisms, 9(6), 1344. https://doi.org/10.3390/microorganisms9061344
  19. Hwang, Y.-H., Park, S., Paik, J.-W., Chae, S.-W., Kim, D.-H., Jeong, D.-G., Ha, E., Kim, M., Hong, G., Park, S.-H., Jung, S.-J., Lee, S.-M., Na, K.-H., Kim, J., & Chung, Y.-C. (2019). Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients, 11(2), 305. https://doi.org/10.3390/nu11020305
  20. Illescas, O., Rodríguez-Sosa, M., & Gariboldi, M. (2021). Mediterranean Diet to Prevent the Development of Colon Diseases: A Meta-Analysis of Gut Microbiota Studies. Nutrients, 13(7), 2234. https://doi.org/10.3390/nu13072234
  21. Khan, M. N., Khan, S. I., Rana, M. I., Ayyaz, A., Khan, M. Y., & Imran, M. (2022). Intermittent fasting positively modulates human gut microbial diversity and ameliorates blood lipid profile. Frontiers in Microbiology, 13, 922727. https://doi.org/10.3389/fmicb.2022.922727
  22. Kim, K. H., Chung, Y., Huh, J.-W., Park, D. J., Cho, Y., Oh, Y., Jeong, H., Yoon, J., Kang, J.-H., Shin, H.-S., Kim, H.-C., Kwon, S.-K., Seo, K. Y., Oh, S. H., Seong, J. K., Ha, S.-J., Nam, K. T., & Kim, J. F. (2022). Gut microbiota of the young ameliorates physical fitness of the aged in mice. Microbiome, 10(1), 238. https://doi.org/10.1186/s40168-022-01386-w
  23. Kleessen, B., Sykura, B., Zunft, H., & Blaut, M. (1997). Effects of inulin and lactose on fecal microflora, microbial activity, and bowel habit in elderly constipated persons. The American Journal of Clinical Nutrition, 65(5), 1397–1402. https://doi.org/10.1093/ajcn/65.5.1397
  24. Le Roy, C. I., Kurilshikov, A., Leeming, E. R., Visconti, A., Bowyer, R. C. E., Menni, C., Falchi, M., Koutnikova, H., Veiga, P., Zhernakova, A., Derrien, M., & Spector, T. D. (2022). Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome. BMC Microbiology, 22(1), 39. https://doi.org/10.1186/s12866-021-02364-2
  25. Lindefeldt, M., Eng, A., Darban, H., Bjerkner, A., Zetterström, C. K., Allander, T., Andersson, B., Borenstein, E., Dahlin, M., & Prast-Nielsen, S. (2019). The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. Npj Biofilms and Microbiomes, 5(1), 5. https://doi.org/10.1038/s41522-018-0073-2
  26. Liu, X., Zou, L., Nie, C., Qin, Y., Tong, X., Wang, J., Yang, H., Xu, X., Jin, X., Xiao, L., Zhang, T., Min, J., Zeng, Y., Jia, H., & Hou, Y. (2023). Mendelian randomization analyses reveal causal relationships between the human microbiome and longevity. Scientific Reports, 13(1), 5127. https://doi.org/10.1038/s41598-023-31115-8
  27. Lourenço, M., Chaffringeon, L., Lamy-Besnier, Q., Pédron, T., Campagne, P., Eberl, C., Bérard, M., Stecher, B., Debarbieux, L., & De Sordi, L. (2020). The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages. Cell Host & Microbe, 28(3), 390-401.e5. https://doi.org/10.1016/j.chom.2020.06.002
  28. Lu, Q., Jiang, Z., Wang, Q., Hu, H., & Zhao, G. (2021). The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation. Annals of Hepatology, 23, 100289. https://doi.org/10.1016/j.aohep.2020.100289
  29. Martínez, I., Lattimer, J. M., Hubach, K. L., Case, J. A., Yang, J., Weber, C. G., Louk, J. A., Rose, D. J., Kyureghian, G., Peterson, D. A., Haub, M. D., & Walter, J. (2013). Gut microbiome composition is linked to whole grain-induced immunological improvements. The ISME Journal, 7(2), 269–280. https://doi.org/10.1038/ismej.2012.104
  30. Melini, F., Melini, V., Luziatelli, F., Ficca, A. G., & Ruzzi, M. (2019). Health-Promoting Components in Fermented Foods: An Up-to-Date Systematic Review. Nutrients, 11(5), 1189. https://doi.org/10.3390/nu11051189
  31. Miller, L., Lehtoranta, L., & Lehtinen, M. (2017). The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis. Nutrients, 9(3), 191. https://doi.org/10.3390/nu9030191
  32. Nagpal, R., Shively, C. A., Register, T. C., Craft, S., & Yadav, H. (2019). Gut microbiome-Mediterranean diet interactions in improving host health. F1000Research, 8, 699. https://doi.org/10.12688/f1000research.18992.1
  33. Nale, J., Redgwell, T., Millard, A., & Clokie, M. (2018). Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model. Antibiotics, 7(1), 13. https://doi.org/10.3390/antibiotics7010013
  34. Natividad, J. M., Lamas, B., Pham, H. P., Michel, M.-L., Rainteau, D., Bridonneau, C., da Costa, G., van Hylckama Vlieg, J., Sovran, B., Chamignon, C., Planchais, J., Richard, M. L., Langella, P., Veiga, P., & Sokol, H. (2018). Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nature Communications, 9(1), 2802. https://doi.org/10.1038/s41467-018-05249-7
  35. O’Toole, P. W., Marchesi, J. R., & Hill, C. (2017). Next-generation probiotics: The spectrum from probiotics to live biotherapeutics. Nature Microbiology, 2(5), 17057. https://doi.org/10.1038/nmicrobiol.2017.57
  36. Ott, S. J., Waetzig, G. H., Rehman, A., Moltzau-Anderson, J., Bharti, R., Grasis, J. A., Cassidy, L., Tholey, A., Fickenscher, H., Seegert, D., Rosenstiel, P., & Schreiber, S. (2017). Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterology, 152(4), 799-811.e7. https://doi.org/10.1053/j.gastro.2016.11.010
  37. Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G. M., Pontifex, M. G., Telatin, A., Baker, D., Jones, E., Vauzour, D., Rudder, S., Blackshaw, L. A., Jeffery, G., & Carding, S. R. (2022). Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. Microbiome, 10(1), 68. https://doi.org/10.1186/s40168-022-01243-w
  38. Podlesny, D., Durdevic, M., Paramsothy, S., Kaakoush, N. O., Högenauer, C., Gorkiewicz, G., Walter, J., & Fricke, W. F. (2022). Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics. Cell Reports Medicine, 3(8), 100711. https://doi.org/10.1016/j.xcrm.2022.100711
  39. Renzella, J. (2018). What national and subnational interventions and policies based on Mediterranean and Nordic diets are recommended or implemented in the WHO European region, and is there evidence of effectiveness in reducing noncommunicable diseases? WHO Regional Office for Europe.
  40. Reynolds, A. N., Akerman, A., Kumar, S., Diep Pham, H. T., Coffey, S., & Mann, J. (2022). Dietary fibre in hypertension and cardiovascular disease management: Systematic review and meta-analyses. BMC Medicine, 20(1), 139. https://doi.org/10.1186/s12916-022-02328-x
  41. Rinott, E., Youngster, I., Yaskolka Meir, A., Tsaban, G., Zelicha, H., Kaplan, A., Knights, D., Tuohy, K., Fava, F., Scholz, M. U., Ziv, O., Reuven, E., Tirosh, A., Rudich, A., Blüher, M., Stumvoll, M., Ceglarek, U., Clement, K., Koren, O., … Shai, I. (2021). Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain. Gastroenterology, 160(1), 158-173.e10. https://doi.org/10.1053/j.gastro.2020.08.041
  42. Rowland, I. (2022). Can probiotics and prebiotics contribute to healthy ageing? Nutrition and Healthy Aging, 7(1–2), 1–7. https://doi.org/10.3233/NHA-210140
  43. Russell, W. R., Gratz, S. W., Duncan, S. H., Holtrop, G., Ince, J., Scobbie, L., Duncan, G., Johnstone, A. M., Lobley, G. E., Wallace, R. J., Duthie, G. G., & Flint, H. J. (2011). High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. The American Journal of Clinical Nutrition, 93(5), 1062–1072. https://doi.org/10.3945/ajcn.110.002188
  44. Schmidt, T. S. B., Li, S. S., Maistrenko, O. M., Akanni, W., Coelho, L. P., Dolai, S., Fullam, A., Glazek, A. M., Hercog, R., Herrema, H., Jung, F., Kandels, S., Orakov, A., Thielemann, R., von Stetten, M., Van Rossum, T., Benes, V., Borody, T. J., de Vos, W. M., … Bork, P. (2022). Drivers and determinants of strain dynamics following fecal microbiota transplantation. Nature Medicine, 28(9), 1902–1912. https://doi.org/10.1038/s41591-022-01913-0
  45. Segal, A., Zlotnik, Y., Moyal-Atias, K., Abuhasira, R., & Ifergane, G. (2021). Fecal microbiota transplant as a potential treatment for Parkinson’s disease – A case series. Clinical Neurology and Neurosurgery, 207, 106791. https://doi.org/10.1016/j.clineuro.2021.106791
  46. Serra, M. C., Nocera, J. R., Kelleher, J. L., & Addison, O. (2019). Prebiotic Intake in Older Adults: Effects on Brain Function and Behavior. Current Nutrition Reports, 8(2), 66–73. https://doi.org/10.1007/s13668-019-0265-2
  47. Shannon, O. M., Ranson, J. M., Gregory, S., Macpherson, H., Milte, C., Lentjes, M., Mulligan, A., McEvoy, C., Griffiths, A., Matu, J., Hill, T. R., Adamson, A., Siervo, M., Minihane, A. M., Muniz-Tererra, G., Ritchie, C., Mathers, J. C., Llewellyn, D. J., & Stevenson, E. (2023). Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: Findings from the UK Biobank prospective cohort study. BMC Medicine, 21(1), 81. https://doi.org/10.1186/s12916-023-02772-3
  48. Shen, X., Liu, L., Peek, R. M., Acra, S. A., Moore, D. J., Wilson, K. T., He, F., Polk, D. B., & Yan, F. (2018). Supplementation of p40, a Lactobacillus rhamnosus GG-derived protein, in early life promotes epidermal growth factor receptor-dependent intestinal development and long-term health outcomes. Mucosal Immunology, 11(5), 1316–1328. https://doi.org/10.1038/s41385-018-0034-3
  49. Su, J., Wang, Y., Zhang, X., Ma, M., Xie, Z., Pan, Q., Ma, Z., & Peppelenbosch, M. P. (2021). Remodeling of the gut microbiome during Ramadan-associated intermittent fasting. The American Journal of Clinical Nutrition, 113(5), 1332–1342. https://doi.org/10.1093/ajcn/nqaa388
  50. Swanson, K. S., Gibson, G. R., Hutkins, R., Reimer, R. A., Reid, G., Verbeke, K., Scott, K. P., Holscher, H. D., Azad, M. B., Delzenne, N. M., & Sanders, M. E. (2020). The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nature Reviews Gastroenterology & Hepatology, 17(11), 687–701. https://doi.org/10.1038/s41575-020-0344-2
  51. Taur, Y., Coyte, K., Schluter, J., Robilotti, E., Figueroa, C., Gjonbalaj, M., Littmann, E. R., Ling, L., Miller, L., Gyaltshen, Y., Fontana, E., Morjaria, S., Gyurkocza, B., Perales, M.-A., Castro-Malaspina, H., Tamari, R., Ponce, D., Koehne, G., Barker, J., … Xavier, J. B. (2018). Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Science Translational Medicine, 10(460), eaap9489. https://doi.org/10.1126/scitranslmed.aap9489
  52. Tomova, A., Bukovsky, I., Rembert, E., Yonas, W., Alwarith, J., Barnard, N. D., & Kahleova, H. (2019). The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Frontiers in Nutrition, 6, 47. https://doi.org/10.3389/fnut.2019.00047
  53. Toward, R., Montandon, S., Walton, G., & Gibson, G. R. (2012). Effect of prebiotics on the human gut microbiota of elderly persons. Gut Microbes, 3(1), 57–60. https://doi.org/10.4161/gmic.19411
  54. Tsai, Y.-C., Cheng, L.-H., Liu, Y.-W., Jeng, O.-J., & Lee, Y.-K. (2021). Gerobiotics: Probiotics targeting fundamental aging processes. Bioscience of Microbiota, Food and Health, 40(1), 1–11. https://doi.org/10.12938/bmfh.2020-026
  55. Udayappan, S. D., Hartstra, A. V., Dallinga-Thie, G. M., & Nieuwdorp, M. (2014). Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus. Clinical and Experimental Immunology, 177(1), 24–29. https://doi.org/10.1111/cei.12293
  56. Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. BMJ, k2179. https://doi.org/10.1136/bmj.k2179
  57. van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E. G., de Vos, W. M., Visser, C. E., Kuijper, E. J., Bartelsman, J. F. W. M., Tijssen, J. G. P., Speelman, P., Dijkgraaf, M. G. W., & Keller, J. J. (2013). Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. New England Journal of Medicine, 368(5), 407–415. https://doi.org/10.1056/NEJMoa1205037
  58. Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., & Sonnenburg, J. L. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16), 4137-4153.e14. https://doi.org/10.1016/j.cell.2021.06.019
  59. Zhang, T., Li, Q., Cheng, L., Buch, H., & Zhang, F. (2019). Akkermansia muciniphila is a promising probiotic. Microbial Biotechnology, 12(6), 1109–1125. https://doi.org/10.1111/1751-7915.13410
  60. Zinöcker, M., & Lindseth, I. (2018). The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease. Nutrients, 10(3), 365. https://doi.org/10.3390/nu10030365

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