The microbiome generates a vast array of compounds that affect hormone signaling, detoxification, immunity, behavior, and brain function, including memory. As we get older, inflammatory microbiota contribute to decline of organ function and age-related diseases. Can a microbiome transplant from young adults reverse the aging process? Does it present a viable treatment strategy for diseases of aging, such as type 2 diabetes, heart disease, and Alzheimer’s disease?
Fecal microbiota transplant and healthspan
Does leaky gut drive aging?
Does gut dysbiosis drive aging, or is it a consequence of aging? This question remains unanswered. To determine whether and how leaky gut accelerates aging, one could swap the microbiomes of mice with leaky gut and mice without it and then measure changes in blood and brain senescence biomarkers.
In our previous article on symptoms and biomarkers of leaky gut, we reported that aging is associated with greater incidence of leaky gut. Another way of looking at the causal relationship between leaky gut and aging is to perform fecal microbiotra transplant (FMT) from an old donor mouse into a young recipient mouse and see how those changes in the microbiome affect senescence. As it turns out, several experiments have been done to explore how FMT from an old to a young mouse affects the trajectory of aging in the young mice. These investigations reveal strategies and targets for slowing or even reversing the aging process and maximizing healthspan.
Young mice with old microbiomes
Mice are coprophagic—they eat their own poop—so they naturally do FMT all the time. But air exposure at room temperature eventually kills most of these microbes. That’s why we immediately freeze the samples in airtight tubes at minus 80 degrees Celsius [1]. Before FMT, researchers typically pre-treat with an antibiotic cocktail—such as some mixture of metronidazole, vancomycin, neomycin, ampicillin, and so on—so that the FMT “takes” more readily. Mossad’s group found that a mixture of cefoxitin, gentamycin, metronidazole, and vancomycin, followed by clindamycin hydrochloride resulted in a 98% reduction of living cells; flow cytometry showed this lowered the number of fecal bacteria by a factor of 10^3 [2].
Another common model to start with is germ-free (GF) mice; that is, mice that lack a microbiome to begin with. However, according to D’Amato and colleagues, GF mice bear significant abnormalities in BBB structure and integrity and microglial numbers and morphology, which can present a confounder in certain studies [3], depending on what you’re investigating. If you’re looking at immune or endothelial cells, it’s likely not advisable to use GF animals.
Induces leaky gut
First things first: there is evidence that old microbiomes can induce leaky gut. Young GF mice colonized with microorganisms by fecal transfer from aged mice showed higher levels of leakage by the fluorescent tracer out of the gut, as compared to young GF mice with microorganisms from young donor mice [4, 5].
Shorter villi and more fibrosis
Zhang and colleagues performed FMT between young (2-3 month old) and old (16-18 month old) omeprazole-pretreated rats [6]. Young rats with old microbiomes had shorter villi and a larger fibrosis area in the colon. This is probably due to viral and bacterial pathogens, which can cause intestinal barrier dysfunction.
I hypothesize that a loss of microvilli lowers the surface area for secretion of antimicrobial peptides and mucins. The folds protect the barrier – if microbes have to go down alleyways, that is significantly more hostile to invasion of the fortress or castle that is built from intestinal epithelial cells. Loss of these alleys makes the gut more vulnerable to attack.
Worsened eye function and caused CNS inflammation
In a paper published in the journal Microbiome in 2022, Parker and colleagues transferred gut microbiota from 24-month-old aged mice to young mice through FMT. These young mice exhibited worsening retinal protein function, increased intestinal barrier permeability, and age-associated CNS inflammation. FMT of young donor microbiota reversed these detrimental effects [7].
Ages microglia
In 2020, D’Amato et al. published a study in which they performed FMT from aged, 24-month-old donor mice into young, 3-month-old recipient mice. They compared this group with control, young adult mice receiving a young adult FMT, as well as a group of untreated mice. They found that hippocampal microglia acquired an aging-like phenotype [3]. Specifically, they saw increased expression of F4/80, a macrophage marker and typical trait of the aging brain, in glia in the white matter of the hippocampus fimbria [3].
What’s more, in a Nature paper by Mossad and colleagues published in 2022, FMT from old to young mice induced leaky gut and increased N6-carboxymethyllysine (CML)-positive microglia [4, 8]. CML is an advanced glycation endproduct (AGE), associated with aging. In other words, the aged microbiome triggered leaky gut and enabled CML to reach the brain and induce senescence in CNS immune cells of young mice. This shows more undeniable evidence that an aging-related microbiome accelerates host aging, and it suggests that rejuvenating the microbiome may slow down the cellular aging process.
Impaired learning, memory, synaptic plasticity, and neurotransmission
D’Amato and colleagues found that FMT from older into young adult animals impaired spatial learning and memory in the Barnes maze test and novel object recognition (NOR). They also took a one-shot label-free quantitative proteomics approach and found that a large number of proteins involved in lipid metabolism were downregulated in aging. The team hypothesized that shifts in the microbiota might underpin the detrimental effects of aging on multiple health-critical functions [3].
Mossad and colleagues found a GM-derived metabolite that is higher in aged donors, harms learning and memory, modulates inhibitory synaptic transmission, and contributes to brain aging in mice. This compound, delta-valerobetaine (delta-vb), reaches the brain, is a precursor of trimethylamine (TMA), and structurally resembles a microbiota-generated metabolite of dietary L-carnitine.
The researchers did FMT between young, 8-week-old, and aged, 15-16-month-old mice pre-treated with an antibiotic cocktail. They then did 16S rRNA sequencing on mouse feces to compare microbiome differences. Additionally, mice underwent behavioral testing and EEG recordings were taken.
To establish a mechanistic link, mice received intraperitoneal (IP) delta-vb and were tested on behavior an hour later with T-maze and NOR. Treated mice did worse than vehicle-treated controls. Elegantly, the group showed that treating aged mice with a young microbiota with this metabolite abrogated improvements in learning and memory. This revealed that delta-vb was driving the cognitive impairment phenotype.
Electrophysiological recordings of mPFC revealed that delta-vb increased frequency of spontaneous IPSCs. This suggested that the metabolite mediates increased inhibition onto cortical pyramidal neurons. They concluded that delta-vb negatively impacts spatial working memory and intermediate term memory. The precise mechanism has yet to be elucidated [2].
Aged FMT into young mice lowered glucose transport-related proteins and brain glucose, and impaired synaptic plasticity and neurotransmission-related proteins in the hippocampus. Proteomic and protein network analyses pointed to differentially expressed proteins in the hippocampus, a brain region heavily affected by aging. On the Barnes maze test, aged FMT displayed impaired learning and memory and NOR—they spent less time with novel object and took longer to approach the escape tunnel of the maze [3].
Lower hippocampal neurogenesis and vagal activation
Rei and colleagues compared FMT of aged (18-20 month old) mice into young (10-12 week old) mice with a control group of young donor FMT into young recipients. FMT from aged mice into young mice decreased adult neurogenesis, decreased novelty-induced neuronal activation, and impaired hippocampus-dependent memory.
They found that FMT of aged into young mice downregulated novelty-induced c-Fos activation in dorsal CA1, CA3, and dentate gyrus compared to controls. It also increased astrogliosis and decreased adult hippocampal neurogenesis as measured by doublecortin (DCX) expression in immature adult-born neurons in the DG. They achieved similar results with mice with humanized microbiomes. With age-associated GM, they saw a reduction in c-Fos+ neurons in the vmNTS (a proxy for activity in the vagus nerve’s nucleus of the solitary tract). They concluded that age-associated FMT leads to a deficit in vagus nerve (VN) ascending inputs to brain, both at rest and following VN activation through food and water consumption. Through additional experiments, they also concluded that inhibiting ascending VN activity is necessary and sufficient for the detrimental impact of age-associated GM transplantation on hippocampal memory.
This paper provides a mechanistic link for age-associated, gut microbiome-mediated memory impariment. The hippocampus is particularly vulnerable to the effects of aging. It turns out the vagus nerve plays an important role in memory. NTS is connected with the locus coeruleus and dorsal raphe, which release NE and 5-HT, respectively, to the hippocampus and whole forebrain. Therefore, a decrease in VN activity is detrimental to hippocampal function [9].
Increased susceptibility to atrial fibrillation
In Zhang’s study, young rats with old microbiomes were more susceptible to atrial fibrillation (AFib). Researchers determined that the old microbiomes upregulated LPS and glucose, which led to NLRP3 inflammasome upregulation. Introducing either LPS-RS (an LPS antagonist) or MCC950, a potent selective inhibitor of NLRP3 inflammasome, protected against atrial fibrillation. Overall, LPS and NLRP3 inhibitors reduced susceptibility and duration of AFib. This all suggests that LPS is a cause of AFib.
Proteomics of the proximal colon and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differentially expressed genes (DEGs) were enriched in inflammatory-related pathways. Aged-FMT rats had increased expression of SG15, S100A8, and S100A9. Aged-FMT rats also had higher AFib duration and atrial fibrosis (% of area) and significantly higher atrial expression of NLRP3, pro-caspase-1, and activated caspase-1 [6], suggesting an aged microbiome could negatively impact heart function.
Does healing leaky gut slow or reverse aging?
How much can restoring the gut lining slow aging? Nutraceuticals and fecal microbiota transplantation (FMT) are two approaches being tested for their therapeutic value in treating leaky gut. If a treatment increases tight junction expression in intestinal epithelial cells, increases mucus production in colonic enterocytes, facilitates a metabolically-balanced microbiome, and promotes appropriate proliferation of stem cells to turn over and replenish the gut lining, chances are good it’s healing leaky gut. Scientists may evaluate whether a treatment is returning functional biomarkers of gut health to a more favorable profile. They can also measure protein expression in various target tissues of interest to evaluate whether the approaches target other outcomes of interest as well, such as brain function.
As it turns out, scientists have given old mice the microbiota of young mice and found that it decreases immune cell aging (so-called “immunosenescence”), improves functional biomarkers of cells of interest in the GI tract, immune system, eyes, and brain, and lengthens healthspan and lifespan.
Old mice with young microbiomes
FMT from young into aged mice has been shown to have significant anti-aging effects, promoting healthspan and increasing lifespan [1]. It was hepatoprotective and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity, and the intestinal barrier.
Healed the gut barrier and increased goblet cells and mucins
Numerous experiments have shown that FMT from young into old animals restores intestinal barrier structure in the old animals. This rejuvenation technology has been replicated multiple times.
Parker found that giving aged mice microbiota from young mice reduced circulating concentrations of LBP to levels comparable to young mice [7]. LBP is a key leaky gut biomarker.
Ma and colleagues have explored both FMT and the probiotic Akkermansia muciniphila (AKK) in separate 12-week-long interventions. Muc2 immunofluorescence staining and ileal ZO-1 and occludin Western blots yielded the following results: FMT significantly increased number of ileal goblet cells and upregulated mucin-2, ZO-1, and occludin, indicating the epithelial barrier function improved. Corroborating these findings, RNA-seq transcriptomics revealed that FMT dramatically increased expression of genes involved in goblet cell differentiation and antioxidative process in the ileum. A. muciniphila and its postbiotic, sodium acetate, had a similar effect. Sodium acetate also increased ileal antioxidant genes and lowered serum IL-6 [1].
Zhang showed that rats colonized with youthful microbiota experienced restored intestinal structure and lower plasma LPS. These rats also had longer villi length in the proximal colon, decreased fibrotic area in the proximal colon, and significantly lower FITC-dextran compared with aged FMT controls [6]. This finding corroborates human studies in which shorter villi and excess fibrosis were observed in colon tissue of elderly human patients.
In another similar FMT study, Zeng and colleages found more goblet cells in FMT young-into-aged mice. Intestinal barrier integrity was improved with treatment with young gut microbiota, as measured by blood FITC-dextran. All this evidence taken together suggests that FMT can help restore intestinal barrier function in older individuals.
Even a probiotic cocktail of four bacterial strains (ProBiotic-4, discussed in the next section) has been shown to be sufficient to mitigate damage in the ileum: hematoxylin-eosin (HE) staining showed that treated mice had less mucus layer atrophy, crypt loss, and villus fracture. It also significantly upregulated tight and adherens junctions proteins in aged mice, signs of healing leaky gut [10].
Changes in the microbiome
Aged mice with young microbiota were significantly enriched in Bifidobacteria, Eubacteria, and Akkermansia [1]. They also had upregulated B vitamin biosynthesis and lipid synthesis. That said, it is unclear how much of B vitamin production by gut microbiota is accessible by the host [7].
Cyanobacteria and Firmicutes were enriched in gut microbiota of young mice, as well as in aged mice given a young microbiota, or young-into-aged mice (FMT-YA). Actinobacteria were enriched in FMT-AA mice and aged mice. On a genus level, FMT-YA mice exhibited increments in Butyricicoccus and Lachnospiraceae [11]. This indirectly suggests a possible increase in butyrate production.
Higher glucose sensitivity
Ma et al. also performed glucose tolerance tests (GTT). They found older mice had higher fasting blood glucose insensitive to glucose insult. FMT from young mice improved glucose sensitivity compared to old controls, but it was only partially restored in comparison to the young group [1]. Interestingly, FMT of young into old mice upregulated FoxO, a downstream regulator of the insulin pathway [11]. Further, Zhang showed that aged rats with impaired glucose tolerance experienced restored glucose tolerance when given youthful microbiota [6].
Improved biomarkers of retinal function
Parker et al. also looked at systemic and tissue-specific biomarkers of inflammation in the eye. Old mice receiving the rejuvenating FMT had improved expression of retinal proteins and reduced inflammatory signaling in the retina [7].
Lowered microglial activation
Microglia are a type of phagocyte, or immune cell that eats invaders, as part of the innate immune system. During leaky gut, phagocytes mount a nonspecific immune attack that can destroy healthy tissues in the crossfire [12]. This damaging process can trigger oxidative stress, which contributes to neurotoxicity and cognitive decline [13].
Parker and colleagues found that old mice receiving young microbiota had significantly decreased activated Iba1+ microglia in the cortex, while the young mice receiving old microbiota had the opposite [7]. A probiotic cocktail was also shown to decrease glial activation and lower gliosis in the CA1 of the hippocampus [10].
Neuroprotective and improved memory
Leaky gut is implicated in cognitive impairment, while restoring intestinal barrier function could reverse these symptoms. In Mossad’s study, FMT from young into aged mice reversed cognitive deficits. These mice experienced an accompanying drop in brain delta-vb to levels comparable to young animals [2].
Yang and colleagues took a slightly different approach, assessing whether administering a probiotic cocktail could improve memory deficits in aged SAMP8 mice. SAMP8 mice are a widely used mouse model of aging and dementia that start developing early cognitive dysfunction and neuronal injury at 9 months old. 9-month-old SAMP8 mice were orally administered ProBiotic-4 at a dose of 2x10^9 colony-forming units (CFU) per day for 12 weeks. ProBiotic-4 is a cocktail composed of Bifidobacterium lactis (50%), Lactobacillus casei (25%), Bifidobacterium bifidum (12.5%), and Lactobacillus acidophilus (12.5%). From 8 weeks on, this probiotic cocktail improved short-term working memory deficits and cerebral neuronal and synaptic injuries. What’s more, ProBiotic-4 significantly preserved neuronal survival in the cortex and CA-1 of the hippocampus. It also rescued SYN expression, a sign of improved synaptic plasticity [10].
Of insulin and indoles: changes to the metabolome, healthspan, and lifespan
Ma et al. found FMT and A. muciniphila consistently increased acetic acid. They then wanted to know if acetic acid could increase lifespan. They administered sodium acetate to C. elegans, a nematode model that is amenable to lifespan studies. Sodium acetate at 40 mg/L and 80 mg/L significantly increased lifespan and healthspan of C. elegans treated with the reactive oxygen species (ROS)-inducer paraquat, as measured by pumping frequency and body bends [1]. They found that sodium acetate downregulated daf-2 (nutrient-sensing insulin / IGF receptor), acted via Daf-16 (homologous to FoxO), and improved gut barrier, intestinal inflammation, and redox status.
Zeng’s team analyzed the metabolomes of old animals given a young microbiome. Aromatic amino acid pathways related to phenylalanine, tyrosine, and tryptophan and other indoles were enriched [11]. Zeng’s team also found that Lachnospiraceae are positively correlated with tryptophan, indole, and indole derivatives. Supplementing animals with tryptophan and indole-3-carbinol (I3C) enhanced numbers of white blood cells (WBCs) in bone marrow. Lachnospiraceae could also produce SCFAs that promote GI repair. Furthermore, Lachnospiraceae and tryptophan-associated metabolites promoted recovery of hematopoiesis and rejuvenated aged hematopoietic stem cells (HSCs) [11]. Their results also suggest that tryptophan, Ganoderma (reishi), DHA, butyrate-generating foods, indole-rich foods (broccoli and other cruciferous veggies), and upregulating glutathione metabolism and serotonin signaling may boost lifespan.
B cell and immune cell composition changes
Ma’s team found that A. muciniphila enriched pathways for B cell receptor signaling, phagocytosis, regulation of leukocyte or lymphocyte activation, and S100a8, related to the innate immune response. A. muciniphila administration downregulated S. aureus infection and NOD-like receptor signaling pathways, and it may play a role in PD and AD [1].
As people get older, there’s an inflammatory myeloid bias and a decrease in lymphoid cells. Zeng et al. found that FMT rebalances age-related immune alterations, specifically changing numbers of immune cells. Aged mice with young microbiomes had increased B cells and CD8+ T cells and decreased myeloid cells. Overall, they saw an increase in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. B cells accounted for the higher percentage of hematopoietic lineages. There were more B cells in animals with a young than an old microbiome. Cell cycle related genes were upregulated in FMT-YA mice, suggesting possible enhanced proliferation / self-renewal of specific immune cells [11]. B cells play an important role in the aging process and are now an area of interest with respect to the microbiome, due to the influence of the microbiome on B cell gene expression, with possible implications for cancer therapies.
Decreased liver toxicity and upregulated antioxidant genes
FMT-YA lowered serum ALT and AST, biomarkers of liver damage, and preserved expression of the antioxidant genes Nrf2 and glutathione peroxidase (Gpx) in liver and ileum. A. muciniphila had a similar effect on antioxidant genes in old mice [1].
Lowered DNA damage, improved vascular function, and preserved blood-brain barrier
Yang et al.’s probiotic cocktail also attenuated age-related disruption of the intestinal barrier and BBB, lowered inflammation, and decreased gamma-H2AX and 8-OHdG, two markers of oxidative DNA damage. It also significantly improved BBB integrity, as measured by claudin-5 and VE-cadherin, and lowered brain LPS [10].
Prevented atrial fibrillation
Zhang et al. found that rats colonized with youthful microbiota experienced restored atrial NLRP3-inflammasome activity, which suppressed development of age-related atrial fibrillation [6].
Connecting the dots: Leaky gut’s effect on aging
Untreated leaky gut, accompanied by lack of changes to diet and lifestyle, can have consequences for metabolism, detoxification, the immune system, brain health, and lifespan.
Leaky gut allows LPS to infiltrate the body and activate inflammation.
A compromised intestinal barrier allows numerous molecules to translocate into the bloodstream, including LPS, lipotechoic acid (LTA), TMAO, delta-vb, and carboxymethyllysine (CML). A potent pathogen-associated molecular pattern (PAMP) [6], LPS strongly provokes inflammation. Microbes could also be exporting their products from the gut to the brain via microvesicles, which can cross the blood-brain barrier (BBB) [7].
LPS can trigger programmed cell death in the host.
In a mechanism established in rodents, LPS and LTA bind to CD14-TLR4 receptor, activating it, which activates the MyD88 pathway. This, in turn, upregulates NF-kB, a transcription factor that activates the NLRP3 inflammasome. This results in caspase-1 cleavage and caspase-18 activation [6], both of which are associated with apoptosis.
Leaky gut is linked with Alzheimer’s disease and cognitive decline.
PET scan data has revealed a link between circulating LPS and amyloid beta deposition in Alzheimer’s disease. Marizzoni and colleagues used PET scans to measure brain amyloidosis in 89 elderly people and correlated them with blood LPS, SCFAs, and inflammation biomarkers. The team found amyloid standardized uptake value (SUVR), a measure of amyloid metabolism, was positively associated with blood LPS, acetate, valerate, and biomarkers of endothelial dysfunction; it was negatively correlated with butyrate and IL-10. Valerate was associated with cognitive impairment [14]. What’s more, LPS has been detected in brain autopsies of patients with AD. LPS co-localizes with AB42 peptides and amyloid beta positive neurons, accumulating around the nucleus. LPS is also highly enriched in the cortex and CA1 hippocampus of AD patients compared to controls [14].
Leaky gut impairs neuronal protein trafficking and signaling.
On a sub-cellular level, LPS binds to plasma membranes, nuclear membranes, and microtubule components. This impairs transcription and translation of neurofilament light (NfL) and downregulates synaptic (SYN), a cytoskeletal element [15]. Because cytoskeletal elements are vital to the healthy functioning of neurons (including transport of organelles and proteins), LPS resultantly hinders neurotransmission and synaptic plasticity, which can give rise to cognitive difficulties [8].
Leaky gut damages mitochondria, alters glucose metabolism, drives aging, and influences lifespan [8, 12].
In a Nature Neuroscience paper, Mossad and colleagues demonstrate that leaky gut allows microbiome-derived CML, an advanced glycation endproduct (AGE), to translocate into the bloodstream, spread to the brain, and damage microglial mitochondrial structures. Specifically, CML increases reactive oxygen species (ROS) and oxidative stress, decreases metabolic activity, and reduces cellular ATP stores in macrophages and microglia. In aged specific pathogen-free (SPF) mice, increased cellular ROS was coupled to Hif1a transcription, driving a shift towards glycolysis. This leads to microglial dysfunction, neuroinflammation, aging, and neurodegeneration. Overall, they conclude that microbiota signals microglia in aging, which could modulate synapses [3]. Thus, maintaining gut integrity is essential not only for digestive health but also for mitigating age-related conditions and preserving cognitive function.
What to eat for healthy gut and brain aging
Turning back the clock on metabolism starts with the gut – particularly balancing microbes and healing leaky gut. Rejuvenation technologies such as nutraceuticals and FMT could slow aging and promote neurological health by introducing therapeutic microbial products and other compounds into the bloodstream. By rebalancing the microbiome’s composition and metabolic activity, you can promote healthy biochemical functions throughout the body. Changing the microbiota ecosystem could buffer against inflammaging by directing immune system towards the gut as opposed to distal tissue [16]. That said, FMT has a long way to go with regards to clinical testing, as serious side effects such as infections have been documented.
Gram-negative bacteria express LPSs as part of their immune defense. As such, LPS is likely here to stay, and it is impractical to use antibiotics chronically. Here are some alternative general suggestions for nutrients and foods to consume to promote intestinal barrier integrity and to slow aging. We will cover more specific nutrients and strategies for restoring gut barrier integrity in an upcoming feature.
Eat omega-3s and other essential fatty acids.
Dietary interventions can influence neuroinflammation. Monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs) impact microglial function. It is advisable to eat omega-3s, particularly DHA, EPA, and ALA, not only for brain health but for gut health. Look for supplements with a high ratio of omega-3s to omega-6s, such as flax seed oil, cod liver oil, or algae-sourced omega-3s.
Additionally, palmitate has anti-inflammatory effects in microglia [7], but it should be noted the physiological effects are likely dose-dependent, as this is a type of saturated fatty acid. All-in-all, fatty acids should be consumed in moderation.
Consume an anti-inflammatory diet.
Anti-inflammatory diets are beneficial for brain and gut health. That is, eat foods that inhibit NLRP3 activation and promote intestinal and endothelial cell integrity. These NF-kB-inhibiting foods and herbs include blueberries, ginger, cacao, green tea, oregano, coffee, thyme, clove, and walnut.
Incorporate probiotics.
A probiotic cocktail was shown to be beneficial for numerous outcomes. Try a probiotic-rich yogurt that contains Lactobacillus casei, L. acidophilus, Bifidobacterium lactis, and B. bifidum cultures.
Have tryptophan- and indole-rich foods.
Consume tryptophan- and other indole-rich foods, such as broccoli and other cruciferous vegetables. These types of foods not only upregulate glutathione metabolism but also serotonin signaling pathways, both of which may boost lifespan.
Obtain butyrate-generating foods.
Eating butyrate-rich foods could preserve blood-brain-barrier integrity [14]. Try Ganoderma (reishi). This food source may increase levels of SCFAs.
Eat low-glycemic index foods.
Insulin signaling is an important determinant of lifespan. Slowing aging importantly can involve making dietary choices to eat low-glycemic foods and maintain a healthy level of glucose sensitivity.
Highlights
An aged microbiome has been demonstrated in young adult subjects to shorten intestinal villi, cause intestinal fibrosis, worsen eye function, increase CNS inflammation, age microglia, impair learning and memory, affect synaptic plasticity and neurotransmission, lower hippocampal neurogenesis and vagal activation, and increase susceptibility to atrial fibrillation.
A youthful microbiome has been shown in aged subjects to restore intestinal barrier function, increase glucose sensitivity, improve eye and liver function, lower microglial activity, improve memory, increase B cell populations, decrease DNA damage, improve cardiovascular function, preserve the blood-brain barrier, and extend healthspan and lifespan.
Overall, leaky gut causes translocation of microbial products, which triggers systemic inflammation and senescence and damages microglial mitochondria. It also can trigger neuronal apoptosis and influence subsequent neurodegenerative disease.
To improve gut and brain health and slow aging, one may consume omega-3s, anti-inflammatory foods, probiotics, and tryptophan- and indole-rich foods, and low glycemic index foods.
Fecal microbiota transplant and healthspan data is limited in clinical populations, and more research is needed before it can be implemented in a widespread way for therapeutic applications.
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This was part 3 of a 5-part leaky gut series. Stay tuned as we cover more important topics related to the microbiome, leaky gut, and restoring the intestinal lining to improve absorption, functional nutrition, energy, and mental performance.
Fecal microbiota transplants, probiotics, and foods for healthspan
Diseases and causes of leaky gut
How to restore the gut barrier
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