The Gut Microbiome's Systemic Impacts

The gut microbiome's impacts on the whole body, including on other body site's microbiomes.

General:

Review, 2020: Intestinal Dysbiosis in, and Enteral Bacterial Therapies for, Systemic Autoimmune Diseases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655733/

Bacterial sensing via neuronal Nod2 regulates appetite and body temperature (Apr 2022, mice) https://www.science.org/doi/10.1126/science.abj3986 "These findings demonstrate that a direct dialog occurs between the gut microbiota and the brain" https://archive.ph/5GBEi

"These results indicate that the commensal mycobiome may be a crucial factor in gut and systemic immunological disorders, based on systemic diffusion of either cytokines, fungal products or metabolites, or micromycetous translocation" (2018): http://www.mdpi.com/2076-2607/6/1/22/htm

"They suggest that ASD likely develops in children due to a gut microbiome impact on the detoxification process in the gut. And this, in turn, allows environmental toxins to enter the bloodstream where they injure mitochondria in brain cells, leading to symptoms related to ASD." (Oct 2020) https://medicalxpress.com/news/2020-10-evidence-link-gut-microbe-deficiency.html

Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease (2018): http://www.clinsci.org/content/132/5/509

Bacterial Dissemination to the Brain in Sepsis. When Sepsis Patients Face Brain Impairment, Is Gut Bacteria to Blame? (2018): https://labblog.uofmhealth.org/lab-report/when-sepsis-patients-face-brain-impairment-gut-bacteria-to-blame - https://www.atsjournals.org/doi/abs/10.1164/rccm.201708-1559OC

Gut Microbiome Diversity Predicts Blood Infections in Pediatric Patients With Cancer (2018): http://www.ajmc.com/newsroom/gut-microbiome-diversity-associated-with-blood-infections-in-pediatric-patients-with-cancer

Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis https://doi.org/10.1186/s40168-018-0578-1 Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis (2018).

Antibiotics Increase Mouse Susceptibility to Dengue, West Nile, and Zika. The authors suggest the antibiotics may have compromised the animals’ immunity by altering their microbiomes. https://www.the-scientist.com/?articles.view/articleNo/52157/title/Antibiotics-Increase-Mouse-Susceptibility-to-Dengue--West-Nile--and-Zika/

Gut microbiota and host defense in critical illness (2017): https://doi.org/10.1097/MCC.0000000000000424

Oral antibiotics for systemic infections/symptoms.

Bones:

Article: Bone and the Microbiome Have a Brittle Relationship. Animal studies and a few small clinical trials show it’s possible to get commensal microbes to protect against bone loss, rather than contribute to it. (July 2019) https://www.the-scientist.com/news-opinion/bone-and-the-microbiome-have-a-brittle-relationship-66116

Review, 2023: Gut Microbiome - Should we treat the gut and not the bones? https://www.journal-cot.com/article/S0976-5662(23)00057-7/fulltext

Commentary, 2019: A Link between the Gut and Bone: Bone Health Impacted by Changes in Gut Microbiota https://doi.org/10.1016/j.ajpath.2018.11.004

Review, 2018: Gut Microbiome and Bone: https://www.sciencedirect.com/science/article/pii/S1297319X18300617

Review, 2018: Bone and the gut microbiome: a new dimension http://jlpm.amegroups.com/article/view/4607

Review, 2017: Gut Microbiota, Immune System, and Bone https://link.springer.com/article/10.1007%2Fs00223-017-0331-y

Review, 2017: From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone https://link.springer.com/article/10.1007%2Fs00223-017-0321-0

Bone loss is ameliorated by fecal microbiota transplantation through SCFA/GPR41/ IGF1 pathway in sickle cell disease mice (Nov 2022) https://www.nature.com/articles/s41598-022-25244-9

Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function (Sep 2022) https://www.sciencedirect.com/science/article/pii/S2214031X22000791

Scientists identify gut bacteria linked to bone density, strength (Sep 2023) https://hms.harvard.edu/news/gut-microbiomes-role-skeletal-health A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.

Analysis of the associations between the human fecal microbiome and bone density, structure and strength: the MrOS cohort (Feb 2022, N = 831) https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4518 "Our findings bolster the view that the gut microbiome is associated with clinically important measures of bone health"

The gut microbiota is a transmissible determinant of skeletal maturation (Jan 2021, mice) https://elifesciences.org/articles/64237

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Post‐Pubertal Skeletal Growth and Maturation (Jan 2020, mice) https://www.eurekalert.org/pub_releases/2020-01/muos-btt012820.php

Unintended side effects: Antibiotic disruption of the gut microbiome dysregulates skeletal health (Jan 2019, mice) https://medicalxpress.com/news/2019-01-unintended-side-effects-antibiotic-disruption.html - Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development https://doi.org/10.1016/j.ajpath.2018.10.017

Components of the Gut Microbiome that Influence Bone Tissue‐Level Strength (May 2021, mice) https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4341

Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation (2017): https://stemcellres.biomedcentral.com/articles/10.1186/s13287-017-0670-7

Mechanisms of gut microbiota-mediated bone remodeling (2018): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914914/

Linking the Gut Microbiota to Bone Health in Anorexia Nervosa (2018): https://link.springer.com/article/10.1007%2Fs11914-018-0420-5

Gut Microbiota and Bone Health (2017): https://link.springer.com/chapter/10.1007/978-3-319-66653-2_4

Immunology of Gut-Bone Signaling (2017): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749247/

Osteomicrobiology: A New Cross-Disciplinary Research Field (2017): https://link.springer.com/article/10.1007/s00223-017-0336-6

Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities. (2018) http://www.mdpi.com/1420-3049/23/7/1517/htm

The gut microbiome and immune systems influence bone growth after mild TBI (Dec 2021) https://www.monash.edu/medicine/news/latest/2021-articles/the-roles-of-the-gut-microbiome-and-immune-systems-on-bone-growth-after-mild-tbi Gut microbiome depletion and repetitive mild traumatic brain injury differentially modify bone development in male and female adolescent rats.

Bacteria in Children’s Throats Found Strongly Associated with Bone and Joint Infections: https://www.genengnews.com/topics/translational-medicine/bacteria-in-childrens-throats-found-strongly-associated-with-bone-and-joint-infections/ - Association between oropharyngeal carriage of Kingella kingae and osteoarticular infection in young children: a case–control study (2017): https://doi.org/10.1503/cmaj.170127

Probiotics and prebiotics:

Prebiotics, Bone and Mineral Metabolism (2017): https://link.springer.com/article/10.1007/s00223-017-0339-3

Prebiotics and Bone (2017): https://link.springer.com/chapter/10.1007/978-3-319-66653-2_10

Prebiotics, Probiotics, and Synbiotics Affect Mineral Absorption, Bone Mineral Content, and Bone Structure (2007): https://academic.oup.com/jn/article/137/3/838S/4664776

Probiotics (Lactobacillus reuteri 6475) can protect the skeletons of older women. The women who received the powder with active bacteria had lost only half as much bone in the skeleton compared with those who received inactive powders (2018): https://archive.fo/ApXtC

Probiotics (Lactobacillus rhamnosus GG) increase bone volume in healthy mice (2018): https://medicalxpress.com/news/2018-11-probiotics-bone-volume-healthy-mice.html

The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression (2018): http://dx.doi.org/10.1016/j.immuni.2018.10.013

Eyes:

Review, Aug 2024: The Relationship Between Gut Microbiome and Ophthalmologic Diseases: A Comprehensive Review https://www.cureus.com/articles/279212-the-relationship-between-gut-microbiome-and-ophthalmologic-diseases-a-comprehensive-review#!/

Review, Sep 2023: Elucidating the Role of the Microbiome in Ocular Diseases https://ajp.amjpathol.org/article/S0002-9440(23)00313-9/fulltext

Review, Nov 2021: The gut microbiota in retinal diseases https://www.sciencedirect.com/science/article/pii/S0014483521004334

Fecal Microbial Transplant in Individuals with Immune-mediated Dry Eye (Jun 2021, n=10, Sjögren's) https://www.ajo.com/article/S0002-9394(21)00348-2/fulltext "Five individuals subjectively reported improved dry eye symptoms 3 months after FMT"

Eye diseases long thought to be purely genetic might be caused in part by bacteria that escape the gut and travel to the retina (Feb 2024, mice) https://www.nature.com/articles/d41586-024-00562-2 CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

Alterations in the gut bacterial microbiome in fungal Keratitis (inflammatory disease of the eye) patients (2018): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199640 - "Our study demonstrates dysbiosis in the gut bacterial microbiomes of FK patients compared to HC. Further, based on inferred functions, it appears that dysbiosis in the gut of FK subjects is strongly associated with the disease phenotype with decrease in abundance of beneficial bacteria and increase in abundance of pro-inflammatory and pathogenic bacteria"

Alterations in gut bacterial and fungal microbiomes are associated with bacterial Keratitis, an inflammatory disease of the human eye (2018): https://www.ncbi.nlm.nih.gov/pubmed/30541945

Gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis. (2018): https://link.springer.com/chapter/10.1007%2F978-3-319-75402-4_53 | And Gut Fungal Microbiome in Uveitis (2019): https://iovs.arvojournals.org/article.aspx?articleid=2730240

Lungs:

Review, Jul 2020: Gut microbiome a promising target for management of respiratory diseases https://portlandpress.com/biochemj/article-abstract/477/14/2679/225933/Gut-microbiome-a-promising-target-for-management

Fungus from the intestinal mucosa can affect lung health. Our microbiome can impair our immune system through the harmless fungus Candida albicans. https://eurekalert.org/pub_releases/2019-02/uoc-fft022219.php. Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans (Feb 2019).

Can We Restore the Lung Microbiome with Fecal Microbiota Transplant (FMT)? (2018) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254895/ "This murine model results suggest a potential role and effectiveness of gut FMT as a therapeutic measure for MDR bacterial infection in the lungs"

The [gut] Microbiome Regulates Pulmonary Responses to Ozone in Mice (2018): https://sci-hub.tw/https://doi.org/10.1165/rcmb.2017-0404OC "[gut] microbiome impacts allergic airway responses, including airway hyperresponsiveness, a characteristic feature of asthma. Here we examined the role of the microbiome in pulmonary responses to a non-allergic asthma trigger, ozone. Our data indicate that the [gut] microbiome contributes to ozone-induced airway hyperresponsiveness, likely via its ability to produce short chain fatty acids."

Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT (2018): https://doi.org/10.1182/blood-2018-01-828996 - "Patients with higher abundances of butyrate producing bacteria were a five-fold less likely to develop viral LRTI, independent of other factors (adjusted HR=0.22, 95% CI 0.04 - 0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients."

The Microbiome and Tuberculosis: Early Evidence for Cross Talk (review, 2018): https://doi.org/10.1128/mBio.01420-18

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae (2017): http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006426

Gastrointestinal carriage is a major reservoir of K. pneumoniae infection in intensive care patients (2017): https://doi.org/10.1093/cid/cix270

Muscles:

Mechanisms Involved in Gut Microbiota Regulation of Skeletal Muscle (May 2022) https://www.hindawi.com/journals/omcl/2022/2151191/

Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women (Sep 2021) https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12788

The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets (May 2021) https://www.nature.com/articles/s41598-021-90881-5

Wound healing:

Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 promote infected wound healing via regulation of the wound microenvironment (2024) https://enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/1751-7915.70031

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation (Jul 2021) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248322

Microbiome Imbalances: An Overlooked Potential Mechanism in Chronic Nonhealing Wounds (2019): https://doi.org/10.1177%2F1534734619832754

The microbiome and its relevance in complex wounds (2019): https://www.ncbi.nlm.nih.gov/pubmed/30670371

Role of gut microbiota in intestinal wound healing and barrier function (2018): https://doi.org/10.1080/21688370.2018.1539595

The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial (2017): https://onlinelibrary.wiley.com/doi/pdf/10.1002/dmrr.2970

Microbial Symbionts Accelerate Wound Healing via the Neuropeptide Hormone Oxytocin (2013): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078898

The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor (2013): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058671

"wounds tend to heal faster on a germ-free animal than they do in a mouse full of bacteria. But even more intriguingly, mice with a skin wound that are fed a live probiotic appear to heal faster than those fed dead bacteria. This suggests that our old friend the immune system may be responding to the gut bacterial infusion and somehow stimulating wound healing." - Jack Gilbert & Rob Knight, but no citation provided.

The Gut Microbiome's Systemic Impacts

General:

Bones:

Probiotics and prebiotics:

Eyes:

Lungs:

Muscles:

Wound healing:

Other: