Long-COVID: Could Supporting Gut Health Help?

In this episode of “The Hashimoto’s Doctor Podcast”, we’re diving into the topic of Long COVID and how a special type of medicine called functional medicine might help. We’ll focus on the connection between the tiny living things in our digestive tracts (gut microbiota) and Long COVID, and explain how a healthy gut might be really important for our overall health, especially after getting over a SARS-CoV-2 (the virus that causes COVID-19) infection.

First off, we’ll try to define Long COVID and share some shocking facts about how many people it affects. Then, we’ll chat about some theories on what might cause Long COVID, like issues with the immune system, changes in the gut microbiota, autoimmune responses, problems with blood clotting, and messed up signals in the nervous system.

We’ll also dive deeper into why the gut microbiota is so important, and its different roles. We’ll discuss gut dysbiosis, which is when the balance of the living things in our gut gets thrown off, and how it can make us more likely to get sick with respiratory diseases and mess with our immune response. We’ll talk about how gut dysbiosis might play a part in Long COVID, especially its effects on the nervous system, and how inflammation can mess with the metabolism of an important substance called tryptophan.

Next, we’ll discuss how functional medicine may help fix the balance of the gut microbiota, using things like prebiotics, probiotics, and postbiotics, and why what we eat matters, including foods rich in polyphenols. We’ll talk about how certain types of Bifidobacterium longum (a good bacteria in our gut) might help improve our health markers, and discuss exciting new treatments like microbiota transplantation.

Come along on this journey as we look into how functional medicine might help manage Long COVID by focusing on our gut health. If you’re curious about functional medicine, gut health, and how to manage Long COVID, this episode is a must-listen!

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Table of Contents for References and Summaries

References:

COVID-19 Spotlights Connections Between Disease and Multiple Lifestyle Factors

Enichen, E., Harvey, C., & Demmig-Adams, B. (2023). COVID-19 Spotlights Connections between Disease and Multiple Lifestyle Factors. American Journal of Lifestyle Medicine, 17(2), 231-257. doi: 10.1177/15598276221123005.

Title: COVID-19 Spotlights Connections between Disease and Multiple Lifestyle Factors

• – The SARS-CoV-2 virus (COVID-19) has a significant impact on global human society and may have originated from zoonotic transmission.
• – SARS-CoV-2 enters human cells through the ACE2 receptor and employs host replication machinery for replication and assembly.
• – Dysbiosis of the gut microbiome during SARS-CoV-2 infection weakens gut-barrier integrity and disrupts immune and microbial balance.
• – Lifestyle factors, such as nutrition, exercise, and stress management, play a role in addressing COVID-19-associated dysbiosis.
• – Patients with persistent symptoms after COVID-19 infection (PASC) show dysbiosis similar to patients with chronic fatigue syndrome.
• – Dietary support and bacteriotherapy may promote eubiosis and counteract viral infectivity and inflammation during and after SARS-CoV-2 infection.
• – The gut-lung axis plays a role in the passage of gut and lung products, and gut microbiome dysbiosis increases the risk of respiratory illness.
• – Increased ACE2 levels, especially in older men, may contribute to enhanced disease severity among males.
• – External factors such as unbalanced diet, physical inactivity, chronic stress, and environmental pollutants contribute to impaired immunity and non-resolving inflammation.
• – Lifestyle interventions involving nutrition, exercise, and stress management can be recommended as adjunct treatments to prevent severe disease manifestations of COVID-19.
• – Balanced diets, regular physical activity with adequate recovery, and stress management can reduce inflammation and improve immune defenses.
• – Structural changes, policy interventions, and access to healthcare and health-promoting lifestyle practices are necessary to control emerging infectious diseases and promote public health.

Key Takeaway:

The article highlights the connections between COVID-19 and various lifestyle factors. It emphasizes the importance of addressing dysbiosis, maintaining gut and immune health, and adopting balanced nutrition, regular exercise, and stress management as adjunct treatments to prevent severe disease manifestations of COVID-19. The article also emphasizes the need for public health measures, policy changes, and global management to prevent future pandemics and promote overall well-being.

Adherence to Healthy Lifestyle Prior to Infection and Risk of Post–COVID-19 Condition

Wang, S., Li, Y., Yue, Y., Yuan, C., Kang, J. H., Chavarro, J. E., Bhupathiraju, S. N., & Roberts, A. L. (2023). Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition. JAMA Internal Medicine, 183(3), 232-241. doi: 10.1001/jamainternmed.2022.6555.

Title: Adherence to Healthy Lifestyle Prior to Infection and Risk of Post–COVID-19 Condition

• – The study investigated the association between pre-infection healthy lifestyle and the risk of developing Post-COVID-19 Condition (PCC) among individuals infected with SARS-CoV-2.
• – The study used data from the Nurses’ Health Study II, an ongoing longitudinal cohort of female nurses in the US.
• – The lifestyle factors assessed included healthy BMI, non-smoking, healthy diet, moderate alcohol consumption, regular exercise, and adequate sleep.
• – The study found that adherence to a healthy lifestyle prior to infection was associated with a significantly lower risk of PCC.
• – If all participants had 5 to 6 healthy lifestyle factors, 36.0% of PCC cases could have been prevented.
• – The results were consistent even when PCC was defined as symptoms lasting at least 2 months or having ongoing symptoms at the time of assessment.
• – The study suggested that lifestyle interventions may potentially reduce the risk of developing PCC or alleviate symptoms in individuals with PCC or other post-infection syndromes.
• – Covariates such as age, race/ethnicity, education, income, health care worker status, and history of chronic diseases were adjusted for in the analysis.
• – The study employed Poisson regression to estimate relative risks (RRs) and population attributable risk percentage (PAR).
• – Sensitivity analyses and adjustments were conducted to validate the robustness of the findings.
• – Unhealthy lifestyle factors, such as smoking, physical inactivity, obesity, and alcohol drinking, accounted for a significant proportion of severe COVID-19 cases in the UK population.
• – BMI and sleep showed the strongest association with a lower risk of PCC among the assessed lifestyle factors.
• – Limitations of the study included potential misclassification of SARS-CoV-2 infection and PCC due to self-reporting and the underestimation of asymptomatic cases.

Key Takeaway:

The adherence to a healthy lifestyle before contracting COVID-19 was found to be associated with a significantly lower risk of developing Post-COVID-19 Condition (PCC). Lifestyle factors such as maintaining a healthy BMI and adequate sleep showed the strongest protective association. These findings highlight the potential of lifestyle interventions in reducing the risk of PCC and mitigating symptoms in individuals affected by COVID-19.

Gut and Airway Microbiota Dysbiosis in COVID-19 and Long-COVID

Ancona G, Alagna L, Alteri C, Pastena A, Muscatello A, Gori A, Palomba E, Tonizzo A, Bandera A. Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID. Front Immunol. 2023;[14:10]80043. doi: 10.3389/fimmu.2023.1080043

Title: Gut and Airway Microbiota Dysbiosis in COVID-19 and Long-COVID

• – The gut microbiota plays a crucial role in human health and disease.
• – Gut dysbiosis is associated with increased susceptibility to respiratory diseases and immune response modifications in the lungs (gut-lung axis).
• – Dysbiosis may also contribute to neurological disturbances through the gut-brain axis.
• – Several studies have reported the presence of gut dysbiosis in COVID-19 and its association with disease severity.
• – Longitudinal analyses are lacking, especially for long-term observation in long-COVID.
• – The role of microbiota transplantation and other therapeutic approaches in disease progression and severity is not well understood.
• – Gut and airway dysbiosis may play a role in COVID-19 and long-COVID neurological symptoms.
• – The interpretation of these data could have important implications for future preventive and therapeutic strategies.

Key Takeaway:

The gut and airway microbiota dysbiosis have been observed in COVID-19 patients and are linked to disease severity and long-COVID neurological symptoms. However, further research is needed to understand the mechanisms and develop effective interventions for COVID-19 and long-COVID.

Role of the Microbiota-Gut-Brain Axis in Postacute COVID Syndrome

Gareau MG, Barrett KE. Coronavirus Disease (COVID-19) and Digestive System: Role of the microbiota-gut-brain axis in postacute COVID syndrome. Am J Physiol Gastrointest Liver Physiol. 2023;324(4):G322-G328. doi:10.1152/ajpgi.00293.2022

Title: Role of the Microbiota-Gut-Brain Axis in Postacute COVID Syndrome

• – The article discusses the role of the microbiota-gut-brain (MGB) axis in the development of postacute sequelae of COVID-19 (PASC), also known as long COVID.
• – PASC refers to a collection of symptoms that persist for months or even years after recovering from acute COVID-19.
• – Impaired MGB axis signaling is implicated in the development of PASC and its associated symptoms.
• – The gut microbiome plays a crucial role in regulating cognitive function through the MGB axis.
• – GI symptoms, such as diarrhea, nausea, vomiting, and abdominal pain, are commonly observed during acute COVID-19 infection and in patients with PASC.
• – Changes in the gut microbiome composition, including decreased abundance of beneficial bacteria and alterations in bacteriophages and fungi, have been observed in patients with PASC.
• – Alterations in the gut virome, including viral infections and changes in fungal populations, may contribute to the development of PASC.
• – SARS-CoV-2 directly infects and replicates within intestinal epithelial cells, leading to local inflammatory responses and potential impacts on the gut microbiome.
• – The severity of acute COVID-19 disease does not correlate with the GI manifestations of PASC.
• – Prolonged fecal viral shedding suggests ongoing gut infection and inflammation that could contribute to persistent PASC symptoms.
• – Modulation of the gut microbiota may serve as a novel approach to treat lung disease and reduce the incidence of PASC.
• – Further studies are needed to understand the mechanisms underlying the MGB axis and its role in PASC.

Key Takeaway:

The article highlights the potential involvement of the microbiota-gut-brain axis in the development of postacute sequelae of COVID-19 (PASC). Changes in the gut microbiome composition, as well as alterations in the gut virome, may contribute to the persistence of symptoms in PASC patients. Understanding the MGB axis and its implications in PASC could lead to improved disease management and treatment options.

Dysbiosis of Oral Microbiome and its Association with COVID-19 Symptoms and Long COVID

Haran JP, Cincotta L, Salive MC, Dutta P, Mutaawe S, Anya O, Meza-Segura M, Moormann AM, Doyle DV, et al. Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID. JCI Insight. 2021 Oct 22;6(20):e152346. doi: 10.1172/jci.insight.152346.

Title: Dysbiosis of Oral Microbiome and its Association with COVID-19 Symptoms and Long COVID

• – The study focuses on investigating the association between dysbiosis (imbalance) in the oral microbiome and the duration of COVID-19 symptoms, including long COVID.
• – Dysbiosis in the oral microbiome has been linked to various systemic inflammatory and infectious diseases.
• – Bacteria in the oral cavity can potentially contribute to respiratory infections either directly or indirectly by hindering pathogen clearance and altering immune responses.
• – The study aims to explore whether dysbiosis of the oral microbiome is associated with ongoing symptoms in COVID-19 patients after hospitalization.
• – The researchers collected oral swabs early in the disease course and followed the patients for 4-week and 10-week symptom resolution outcomes.
• – The analysis of oral microbiome composition was done using shotgun metagenomic sequencing.
• – Prevotella species and Gemella sanguinis, known to cause infections, were found to be associated with long COVID.
• – Bacterial abundances in the oral microbiome were able to predict long COVID.
• – Pathway analysis revealed associations with anti-inflammatory molecules and lower levels of branched amino acids in patients with ongoing symptomatic COVID-19.
• – The study suggests that dysbiosis in the oral microbiome may play a role in prolonging symptom duration and contributing to long COVID.
• – The oral microbiome has been found to associate closely with SARS-CoV-2 coinfections in the lungs.
• – The study acknowledges limitations in the number of patients enrolled and calls for further research with larger and more diverse populations.
• – Whole genome sequencing provided greater resolution than 16S rRNA gene sequencing for microbiome analysis.
• – The findings highlight the potential of the oral microbiome in understanding post-infection prolonged syndromes and predicting and preventing the development of long COVID.

Key Takeaway:

The study suggests that dysbiosis in the oral microbiome, characterized by an imbalance in bacterial composition, may contribute to the prolongation of COVID-19 symptoms and the development of long COVID. Understanding the role of the oral microbiome in COVID-19 outcomes could potentially lead to diagnostic and therapeutic approaches for managing long COVID syndrome. Further research with larger and more diverse populations is needed to validate these findings and explore the underlying mechanisms.

Microbiota and COVID-19: Long-term and Complex Influencing Factors

Gang J, Wang H, Xue X, Zhang S. Microbiota and COVID-19: Long-term and complex influencing factors. Front Microbiol. 2022;[13:96]3488. doi:10.3389/fmicb.2022.963488.

Title: Microbiota and COVID-19: Long-term and Complex Influencing Factors

• – COVID-19 affects not only the respiratory system but also other systems like digestive, cardiovascular, nervous, and reproductive.
• – The target of SARS-CoV-2 invasion, angiotensin-converting enzyme 2 (AEC2), is found in the respiratory and gastrointestinal tract.
• – Microbiota dysbiosis, including bacteria, fungi, and viruses, has been observed in patients with COVID-19.
• – The gut microbiota composition in COVID-19 patients shows lower abundance of Bifidobacterium, Collinsella, and Streptococcus, while Bacteroidetes and Enterobacteriaceae are higher. Faecalibacterium and Roseburia depletion is associated with severe/critical cases.
• – Limitations in current studies include a lack of pre-infection and post-clearance gut microbiota characterization, unclear disease stages at sample collection, and small sample sizes.
• – Animal experiments (macaques and hamsters) are being conducted to overcome these limitations.
• – Oropharyngeal microbial disorders and microbiota signatures can be indicators of disease severity and early assessment.
• – The respiratory microbiota in patients with COVID-19 and community-acquired pneumonia differs from healthy individuals, but specific differences are not described.
• – Critically ill patients with COVID-19 show reduced oropharyngeal microorganism diversity and increased antibiotic resistance genes.
• – The upper respiratory tract microbiota of children with COVID-19 shows increased Comamonadaceae and persistent dominance of pathogenic bacterium Pseudomonas.
• – Probiotics and fecal microbiota transplantation (FMT) are being explored as potential treatments for COVID-19, but further study is needed.
• – Traditional Chinese medicine (TCM) integrated with Western medicine has shown positive results in the treatment of COVID-19.
• – ACE2 enzyme activators have potential for metabolic complications and inhibiting SARS-CoV-2 entry.
• – Current studies have limitations in determining if microbiota changes are caused by COVID-19 or other factors, and the mechanisms behind the microbiota’s impact on disease severity need further clarification.

Key Takeaway:

The COVID-19 disease caused by SARS-CoV-2 affects not only the respiratory system but also other body systems. Microbiota dysbiosis, especially in the gut and respiratory tract, has been observed in patients with COVID-19. These microbiota changes may persist even after recovery from the disease and can potentially affect disease severity and prognosis. Further research is needed to understand the relationship between microbiota composition, disease progression, and potential interventions such as probiotics and fecal microbiota transplantation. Integrating traditional Chinese medicine with Western medicine and exploring ACE2 enzyme activators may provide additional avenues for managing the disease and its complications.

Gut Dysbiosis and Long COVID-19: Exploring the Gut-Lung Axis

Giannos P, Prokopidis K. Gut dysbiosis and long COVID-19: Feeling gutted. J Med Virol. 2022 Jul;94(7):2917-2918. doi: 10.1002/jmv.27684. Epub 2022 Mar 7. PMID: 35233795; PMCID: PMC9088471.

Title: Gut Dysbiosis and Long COVID-19: Exploring the Gut-Lung Axis

• – COVID-19 has primarily been considered a respiratory illness, but there is evidence suggesting a potential link between the gut microbiota and long-term complications of the disease.
• – Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be partially explained by certain microbial species contributing to the inflammatory phenotype observed in COVID-19 patients.
• – Dysbiosis of the gut microbiota, characterized by an imbalance in microbial composition, has been associated with poor clinical outcomes in mechanically ventilated COVID-19 patients.
• – Specific bacterial species, such as Granulicatella, Rothia mucilaginosa, Burkholderia cepacia complex, Staphylococcus epidermidis, Mycoplasma hominis, and Mycoplasma orale, have been found to be elevated in the gut microbiome of COVID-19 patients, especially those with severe illness.
• – Disruption of the gut microbiota in COVID-19 patients may explain the cytokine storm-induced complications post-infection.
• – Fecal transplantation, a procedure that aims to restore gut microbiota diversity, has shown promise in bolstering the respiratory system of COVID-19 patients.
• – Long COVID-19 patients exhibit a damaged microbial microenvironment compared to uninfected individuals, indicating persistent alterations in the microbiome even after recovery.
• – Reduced microbial diversity and an increase in pathogenic bacteria have been observed in long COVID-19 patients, possibly contributing to sustained intestinal inflammation during infection.
• – Supplementation of anti-inflammatory bacterial species and fecal transplantation are suggested as potential interventions to accelerate gut microbiota restoration and long COVID-19 rehabilitation.

Key Takeaway:

Emerging evidence suggests a connection between gut dysbiosis and long-term complications in COVID-19 patients. Dysbiosis of the gut microbiota, characterized by an imbalance in microbial composition, may contribute to the inflammatory phenotype observed in severe cases. Restoring a healthy gut microbiome through interventions like fecal transplantation or supplementation of anti-inflammatory bacteria could potentially aid in the recovery of long COVID-19 patients.

Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome

Wang Y, Wu G, Zhao L, Wang W. Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome. mBio. 2022 Apr 26;13(2):e0380121. doi: 10.1128/mbio.03801-21. Epub 2022 Mar 7. PMID: 35254129; PMCID: PMC9040862.

Title: Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome

Key Points:

• – The study focuses on the use of a high-fiber formula (NBT-NM108) to alleviate severe gastrointestinal (GI) symptoms in a patient with post-acute COVID-19 syndrome.
• – Post-acute COVID-19 syndrome refers to ongoing health problems experienced 4 or more weeks after the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• – GI symptoms in COVID-19 patients may be associated with dysbiosis of the gut microbiota.
• – The high-fiber formula is designed to recover a healthier gut microbiota by increasing short-chain fatty acid (SCFA) producers and decreasing proinflammatory and endotoxin-producing bacteria.
• – The patient in the study had severe and persistent GI symptoms, including loss of appetite, nausea, and constipation, for over a year, despite conventional treatments.
• – The intervention involved gradually increasing the dosage of the high-fiber formula over a 2-month period.
• – The high-fiber formula significantly alleviated the severity of GI symptoms, including loss of appetite, nausea, and anxiety.
• – Medication dosage for controlling nausea decreased during the intervention.
• – Blood sample analysis showed improved liver function and stable glucose and lipid metabolism during the intervention.
• – The high-fiber formula reduced fermentation activity in the small intestine, potentially contributing to the alleviation of GI symptoms.
• – Analysis of fecal samples revealed significant structural changes in the patient’s gut microbiota during the intervention.
• – Eighteen amplicon sequence variants (ASVs) of the gut microbiota significantly responded to the nutritional intervention, with six ASVs negatively correlated with symptom severity and medication dosage.
• – The enrichment of SCFA-producing bacteria in the gut microbiota was associated with the alleviation of symptoms.
• – The study suggests the feasibility of nutritional modulation of the gut microbiota as a potential intervention for alleviating GI symptoms in patients with post-acute COVID-19 syndrome.

Key Takeaway:

This study highlights the potential of a high-fiber formula to modulate the gut microbiota and alleviate severe gastrointestinal symptoms in a patient with post-acute COVID-19 syndrome. The intervention resulted in improved symptom severity, reduced medication dosage, and positive changes in the gut microbiota composition. Further research and randomized controlled trials are needed to establish the clinical efficacy and safety of high-fiber interventions in post-acute COVID-19 syndrome.

Neuroimmune Responses to COVID-19 in the Aging Brain: Post-Acute Sequelae and Behavioral/Nutritional Interventions

Müller L, Di Benedetto S. Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions. Immun Ageing. 2023;[20:17]. doi:10.1186/s12979-023-00341-z

Title: Neuroimmune Responses to COVID-19 in the Aging Brain: Post-Acute Sequelae and Behavioral/Nutritional Interventions

• – COVID-19 has a greater impact on older individuals and can lead to long COVID complications.
• – Immunosenescence (age-related remodeling of the immune system) and chronic low-grade inflammation contribute to increased vulnerability in older adults.
• – Neuroimmune interactions with SARS-CoV-2 play a role in the development of persistent long COVID conditions.
• – Psychosocial stress, loneliness, anxiety, and aging can distress the neuroendocrine system, potentially affecting brain health.
• – High levels of cortisol, triggered by the HPA axis, can impair synaptic plasticity, cause neuroinflammation, and contribute to age-related neurobehavioral disturbances.
• – Neuroimmune interactions may serve as a critical link between SARS-CoV-2 infection and mental health impairments.
• – SARS-CoV-2 can bind to the ACE2 receptor, which is expressed in neurons and glial cells, inducing inflammation and the release of reactive oxygen species in the central nervous system.
• – Viral invasion of the brain parenchyma is not well understood, but inflammatory mediators from the choroid plexus may play a role.
• – Approximately 30% of patients develop long COVID, and neuroimmune mechanisms are involved in its pathogenesis.
• – The interplay of viral and host biological factors, including inflammation, autoimmunity, and mitochondrial failure, may contribute to long COVID.
• – Therapeutic interventions for long COVID can include immunomodulatory approaches like nutrition, physical exercise, and stress reduction.
• – Regular physical exercise can improve neuroimmune homeostasis and mitigate mental and psychological impairments associated with long COVID.
• – Aging individuals with a history of COVID-19 and the currently young population who had mild/asymptomatic courses may experience distinctive aging trajectories and heightened neurogenerative conditions in the future.
• – Further research is needed to understand the multidimensional interactions between psychosocial stressors, immunosenescence, neuroinflammation, and SARS-CoV-2, and to develop effective therapeutic and behavioral interventions.

Key Takeaway:

This article explores the impact of COVID-19 on the aging brain and the role of neuroimmune responses in the development of long COVID. It highlights the importance of understanding the mechanisms underlying these interactions and suggests behavioral and nutritional interventions, including exercise and stress reduction, as potential approaches to mitigate the long-term consequences of COVID-19. Further research is needed to fully comprehend the neurological effects of COVID-19 and develop targeted interventions for individuals with persistent symptoms.

Association between Food Intake, Clinical and Metabolic Markers, and DNA Damage in Older Subjects

Del Bo’ C, Martini D, Bernardi S, et al. Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects. Antioxidants (Basel). 2021;10(5):730. doi:10.3390/antiox10050730

Title: Association between Food Intake, Clinical and Metabolic Markers, and DNA Damage in Older Subjects

• – The study investigates the level of DNA damage in older subjects with intestinal permeability and its association with clinical, metabolic, and dietary markers.
• – DNA damage was assessed in peripheral blood mononuclear cells using the comet assay in 49 older subjects.
• – Positive associations were found between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and inverse associations with dietary markers (e.g., vitamin C, E, B6, folates), which varied based on sex.
• – Subjects were selected based on inclusion and exclusion criteria, including age ≥60 years, good cognitive and nutritional status, and increased intestinal permeability.
• – Food intake was collected through weighed food diaries, and energy, nutrient, and polyphenol intake were estimated using software.
• – DNA damage was evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage using the comet assay.
• – The analysis showed positive correlations between H2O2-induced DNA damage and dietary markers such as cholesterol, omega 3 fatty acids, and vitamin B6.
• – Stratifying subjects by sex, significant correlations between DNA damage and dietary markers were observed in women but not in men.
• – The inverse association was found between DNA damage and dietary fiber and vitamins, and positive associations were found with dietary lipids and cholesterol.
• – Polyphenols were reported to have a protective effect against DNA damage, but no significant association was found in this study.
• – Conflicting results in the literature on the association between DNA damage and dietary patterns may be influenced by various confounding factors.
• – Overweight/obesity was positively associated with DNA strand breaks or oxidative DNA damage in previous studies, but no significant association was found in this study.
• – Positive associations were observed between DNA damage and LDL/HDL ratio, total cholesterol/HDL ratio, and uric acid levels in women.
• – No significant relationship was found between serum zonulin levels (marker of intestinal permeability) and DNA damage markers.
• – The study has some limitations, including a small sample size and high inter-individual variability in DNA damage levels.

Key Takeaway:

This study explores the association between DNA damage and clinical, metabolic, and dietary markers in older subjects with intestinal permeability. The findings indicate positive associations between DNA damage and clinical/metabolic markers, and inverse associations with dietary markers, with differences based on sex. The study highlights the importance of further investigations and the development of preventive strategies to understand and mitigate DNA damage in older adults.

Systematic Review on Polyphenol Intake and Health Outcomes: Is there Sufficient Evidence to Define a Health-Promoting Polyphenol-Rich Dietary Pattern?

Del Bo’ C, Bernardi S, Marino M, Porrini M, Tucci M, Guglielmetti S, Cherubini A, Carrieri B, Andres-Lacueva C, Kirkup B, Kroon P, Zamora-Ros R, Liberona NH, Riso P. Systematic Review on Polyphenol Intake and Health Outcomes: Is there Sufficient Evidence to Define a Health-Promoting Polyphenol-Rich Dietary Pattern? Nutrients. 2019 Jun;11(6):1355. doi: 10.3390/nu11061355.

• – The systematic review focuses on the association between polyphenol intake and specific disease markers or endpoints.
• – Polyphenol intake has been linked to reduced risk for chronic diseases, although the effective amount of polyphenols required for such benefits is debated.
• – Tea, coffee, red wine, fruits, and vegetables are identified as the main dietary sources of polyphenols.
• – The estimation of mean total polyphenol intake shows significant heterogeneity across reviewed data.
• – Methodological issues, such as the assessment tools, databases, and polyphenol subclasses, contribute to variations in reported polyphenol intake.
• – Dietary intake measurements are challenging, and single methods may not accurately estimate exposure.
• – Food databases often lack comprehensive information on all polyphenol sources and may underestimate intake due to non-extractable polyphenols.
• – Polyphenol intake varies with age, gender, and country, with different patterns observed depending on region-specific dietary habits.
• – Limited data on polyphenol intake in children and adolescents show a generally low intake, particularly in fruit and vegetable consumption.
• – Polyphenols have potential protective effects on cardiovascular disease (CVD) markers, and certain classes/subclasses may reduce the incidence of type 2 diabetes (T2D) and CVD events/mortality.
• – Polyphenol-rich dietary patterns are suggested as a valuable tool for the prevention of chronic diseases.

Key Takeaway:

The systematic review highlights the growing interest in polyphenol intake and its association with chronic diseases. While there is still debate on the effective amount of polyphenols for health benefits, evidence suggests that certain classes/subclasses of polyphenols may reduce the risk of CVD and T2D. However, the estimation and measurement of polyphenol intake pose challenges due to methodological differences and variations in dietary patterns. Overall, a polyphenol-rich dietary pattern shows potential for promoting health and preventing chronic diseases.

Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects

Martini D, Tucci M, Cherubini A, et al. Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects. Nutrients. 2020;12(8):2458. doi:10.3390/nu12082458

Title: Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects

• – The study aims to evaluate the nutritional composition of nursing home dietary menus and estimate the actual intake of nutrients and polyphenols in older subjects living in a residential care setting.
• – The assessments were conducted as part of the MaPLE project, which investigates the benefits of a polyphenol-enriched diet on intestinal permeability in older subjects.
• – The menus provided in the nursing home were comparable in terms of nutritional composition and aligned with the dietary recommendations for older subjects in Italy.
• – The distribution of macronutrients in the menus was consistent with the recommendations, although there was a higher intake of simple carbohydrates compared to the recommendations.
• – Protein intake mainly derived from animal sources and exceeded the suggested dietary target, while total lipid intake was within the reference range.
• – The study focused on polyphenols as these compounds have the potential to provide specific benefits to the target population.
• – The polyphenol content of the seasonal menus was relatively consistent throughout the year.
• – Actual food consumption indicated a mean polyphenol intake of approximately 660 mg/day, which was lower than some previously reported studies in older subjects.
• – The intake of coffee and wine was limited in the nursing home to reduce associated risks.
• – Increasing polyphenol intake in older subjects is achievable through small amounts of polyphenol-rich food products, and it is well tolerated without adverse effects.
• – Older subjects preferred consuming polyphenol-rich products as mid-morning and afternoon snacks during the intervention.
• – The analysis of polyphenol-rich food consumption may contribute to a better understanding of chronobiological aspects related to the effects of bioactive compounds.
• – Dietary menus for older subjects should be revised to optimize the intake of essential nutrients and bioactive compounds, such as polyphenols, to lower the risk of chronic diseases and improve metabolic and functional activities during aging.
• – Further studies are needed to improve tools for estimating polyphenol intake and to define the amount of polyphenols needed to achieve health benefits in older subjects.

Key Takeaway:

The study evaluates the nutritional composition and polyphenol intake in older subjects living in a residential care setting. The findings highlight the importance of optimizing dietary menus for older subjects to enhance nutrient and bioactive compound intake, such as polyphenols, for better health outcomes. Increasing polyphenol intake through small amounts of polyphenol-rich foods is feasible and well-tolerated in older individuals, with potential benefits for chronic disease prevention and improved metabolic function. Further research is needed to refine dietary guidelines and improve tools for estimating polyphenol intake in this population.

Probiotic Bacteria as Modulators of Cellular Senescence: Emerging Concepts and Opportunities

Sharma R, Padwad Y. Probiotic bacteria as modulators of cellular senescence: emerging concepts and opportunities. Gut Microbes. 2020;11(3):335-349. doi:10.1080/19490976.2019.1697148

Title: Probiotic Bacteria as Modulators of Cellular Senescence: Emerging Concepts and Opportunities

– Probiotic bacteria have multifaceted health benefits and can mitigate age-associated oxi-inflammatory stress, immunosenescence, and gut dysbiosis.

– The accumulation of senescent cells is closely related to the development of aging phenotypes and age-related disorders.

– Eliminating or delaying the development of senescent cells can potentially target age-related diseases.

– Nutritional interventions, such as probiotic supplementation, play a critical role in influencing cellular senescence and the senescence-associated secretory phenotype (SASP).

– Probiotics can attenuate age-associated inflamm-aging, immunosenescence, and oxidative stress, promoting healthy aging and longevity.

– Studies have shown that probiotics can prevent senescence of colon tissue, suppress senescence markers, inhibit inflamm-aging, and restore tissue homeostasis.

– Probiotic bacteria can influence the progression and severity of cellular senescence, potentially impacting tissue homeostasis and health.

– There is a need for further research to identify specific probiotic bacteria or their metabolites with anti-senescence, anti-SASP, senolytic, or immune-enhancing properties.

– Combining probiotic bacteria with polyphenols may offer extensive effects on regulating cellular senescence, aging, and associated pathologies.

Key Takeaway:

Probiotic bacteria have shown promising potential in modulating cellular senescence and aging-related processes. Understanding the mechanisms and identifying specific probiotic strains or metabolites with anti-senescence properties can pave the way for developing probiotic-based therapies for promoting healthy aging and preventing age-related disorders. Further research is needed to explore these opportunities and optimize the combination of probiotics with other bioactive compounds for enhanced effects on cellular senescence.

Mucins, Gut Microbiota, and Postbiotics’ Role in Colorectal Cancer

Gut Microbes. Mucins, gut microbiota, and postbiotics role in colorectal cancer. Gut Microbes. 2021;13(1):PMC8489937. doi: 10.1080/19490976.2021.1879017

Key Points from  Mucins, Gut Microbiota, and Postbiotics’ Role in Colorectal Cancer

– An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, leading to inflammatory diseases and colorectal cancer.

– The colon epithelium protects itself by forming a double mucus layer primarily composed of mucins, which play a crucial role in maintaining intestinal layers and preventing pathogenic organism invasion.

– Dietary patterns can alter the gut microbiota composition, which, in turn, regulates mucin expression and influences the intestinal mucus layer.

– Consumption of a Western-style diet (rich in high-fat calories and low in fiber) and other factors can lead to dysbiosis (microbiota alterations) in the colon, reducing mucus layer thickness and increasing intestinal permeability.

– Administration of prebiotics (such as GOS and FOS) and probiotics (particularly bifidobacteria and lactobacilli) along with a prudent diet can improve intestinal layer functionalities and maintain proper gut health.

– Bacteria in the colon convert dietary fiber into short-chain fatty acids (SCFAs), including butyric acid, which serves as an energy source for the host and helps maintain the mucus layer.

– Mucin-2 (MUC2) is a key mucin secreted from goblet cells, and its expression and degradation by the gut microbiota need to be balanced to ensure proper mucus layer function.

– Dietary factors, especially red and processed meat consumption, are associated with an increased risk of colorectal cancer, while whole grains and dairy products decrease the risk.

– Phytochemicals derived from dietary fiber and microbial metabolites can modulate the gut microbiota, prevent intestinal inflammation, and inhibit the growth of colorectal cancer cells.

– Modulation of gut microbiota through prebiotics (non-digestible carbohydrates) and probiotics (live microorganisms) can protect against colitis and colorectal cancer.

– Postbiotics, the metabolites released by gut microorganisms, play a crucial role in mucin regulation and intestinal mucus layer formation, including short-chain fatty acids and secondary bile acids.

Key Takeaway:

The interaction between mucins, gut microbiota, and postbiotics has a significant impact on colorectal cancer development. Dietary patterns, consumption of prebiotics and probiotics, and the modulation of gut microbiota can play a crucial role in maintaining intestinal health and preventing diseases like colorectal cancer. The balance between mucin expression, degradation, and microbial metabolites is essential for a healthy intestinal mucus layer and overall gut health.

Interactions of Commensal and Pathogenic Microorganisms with the Mucus Layer in the Colon

Cai R, Cheng C, Chen J, Xu X, Ding C, Gu B. Interactions of commensal and pathogenic microorganisms with the mucus layer in the colon. Gut Microbes. 2020;11(4):680-690. doi:10.1080/19490976.2020.1735606

Title: Interactions of Commensal and Pathogenic Microorganisms with the Mucus Layer in the Colon

– The review article focuses on the interactions between commensal and pathogenic microorganisms with the mucus layer in the colon.

– The intestinal mucosal barrier, consisting of epithelial cells and mucus layers secreted by goblet cells, acts as the first line of defense against pathogenic gut microbiota.

– Disruption of the homeostasis between the microbiota and mucus layer can lead to alterations in the gut microbiota and the entry of pathogens into the intestinal mucosal barrier.

– The structures of the colon mucus layer include an outer layer, which is less dense and serves as a habitat for commensal bacteria, and an inner layer that is stratified, attached to epithelial cells, and impermeable to bacteria.

– Mucins, complex agglomerates of heavily O-glycosylated proteins, are the main components of the mucus layer, with gel-forming mucins secreted by goblet cells being the most abundant.

– MUC2 mucin is a major gel-forming mucin synthesized and secreted by goblet cells in the colon, forming large polymeric netlike structures.

– The mucus layer provides a protective effect by regulating the local milieu, providing attachment sites for microorganisms, and secreting antibodies targeting specific microbial antigens.

– Several influencing factors, including diet styles, medications, and host genetics, can disrupt the homeostasis between the microbiota and mucus layer.

– The review also discusses the interactions between pathogenic microorganisms and the mucus layer and commensal microbiota, aiming to unravel underlying pathogenic mechanisms and develop strategies to prevent pathogenic colonization.

– The understanding of these complex interactions under both homeostatic and dysbiosis conditions in the colon is crucial for maintaining gut health.

Key Takeaway:

The mucus layer in the colon plays a vital role in maintaining the balance between commensal and pathogenic microorganisms. Disruption of this balance can lead to alterations in the gut microbiota and compromise the protective function of the mucus layer, allowing pathogens to colonize the intestinal mucosal barrier. Understanding the interactions between microorganisms and the mucus layer is important for developing strategies to prevent pathogenic colonization and promote gut health.

Epithelial GPR35 Protects from Citrobacter rodentium Infection by Preserving Goblet Cells and Mucosal Barrier Integrity

Riedel E, Liberali P, Walser JC, Morales RA, Niess JH, Villablanca EJ. Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity. Mucosal Immunol. 2021 Sep;14(5):1090-1103. doi: 10.1038/s41385-021-00433-4. PMID: 33931762.

Title: Epithelial GPR35 Protects from Citrobacter rodentium Infection by Preserving Goblet Cells and Mucosal Barrier Integrity

– Goblet cells are important for maintaining intestinal health by secreting mucin and creating a protective mucus layer against bacterial infection.

– The molecular pathways regulating goblet cell function are largely unknown, and the role of GPR35 in promoting the epithelial barrier is unclear.

– Epithelial-specific deletion of GPR35 leads to reduced goblet cell numbers in the proximal colon and decreased expression of Muc2, resulting in microbiome alterations and increased susceptibility to Citrobacter rodentium infection.

– GPR35 deficiency in epithelial cells activates caspase-11-mediated pyroptosis in goblet cells, leading to a barrier defect and increased bacterial translocation upon C. rodentium infection.

– Loss of GPR35 in epithelial cells leads to reduced expression of Gfi1 and Spdef, which are crucial factors for goblet cell maturation.

– Genetic deletion of GPR35 specifically in macrophages does not affect protection against C. rodentium.

– The impairment of goblet cells and reduction in Muc2 expression in the proximal colon do not cause spontaneous colitis but may be compensated by NADPH oxidase activity.

– Goblet cells express the highest level of GPR35 among all epithelial cell types, and its deletion mainly affects these cells.

– Epithelial GPR35 plays a critical role in maintaining the barrier integrity by preserving goblet cells, which are essential for defense against intestinal pathogens.

– Pharmacological modulation of GPR35 signaling may be a potential strategy to prevent the breakdown of epithelial barrier integrity in inflammatory bowel disease (IBD) patients.

Key Takeaway:

This study highlights the importance of epithelial GPR35 in protecting against Citrobacter rodentium infection by preserving goblet cells and maintaining the mucosal barrier integrity in the colon. Understanding the relationship between the microbiota and goblet cells, as well as the role of GPR35, may offer promising therapeutic approaches for IBD patients with compromised epithelial barrier integrity.

Postbiotics — When Simplification Fails to Clarify

Aguilar-Toalá JE, Arioli S, Behare P, et al. Postbiotics — when simplification fails to clarify. Nat Rev Gastroenterol Hepatol. 2021;18(11):825-826. doi:10.1038/s41575-021-00521-6

Title: “Postbiotics — When Simplification Fails to Clarify: Key Points”

– The article discusses the nomenclature and definition of postbiotics in relation to the use of inactivated bacteria and their products as health-promoting factors.

– The authors argue that the term “postbiotic” was explicitly defined in 2013 as any factor resulting from the metabolic activity of a probiotic or any released molecule capable of conferring beneficial effects to the host.

– The authors point out that the term “postbiotic” is largely used in accordance with the original definition and not according to the new meaning proposed by the International Scientific Association of Probiotics and Prebiotics (ISAPP).

– A search on PubMed using the term “postbiotics” revealed that only 14% of the papers encompassed inactivated bacteria, suggesting that the majority of publications use the term in line with the original definition.

– The authors propose the term “paraprobiotic” to explicitly indicate inactivated and/or dead bacteria, as it encompasses all descriptions of inactivated cells.

– They argue that there is a scientific need to distinguish well-defined molecular factors of microbial origin with health-promoting properties (postbiotics) from complex matrices derived from microbial cells, for which the precise molecular factors supporting the health benefits are not comprehensively known (paraprobiotics).

– The authors emphasize the importance of clear definitions in science and suggest that there is no need for heterogeneous groups when unique definitions are applicable.

Key Takeaway:

The article highlights the ongoing debate around the definition of postbiotics and the use of inactivated bacteria in health-promoting products. The authors advocate for a distinction between well-defined molecular factors (postbiotics) and complex matrices derived from microbial cells (paraprobiotics). Clear definitions and terminology are essential for accurate communication and understanding in the field of postbiotics.

Long COVID: Major Findings, Mechanisms, and Recommendations

Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. Published online January 13, 2023. doi: 10.1038/s41579-022-00846-2.

Title: Key Points from “Long COVID: Major Findings, Mechanisms, and Recommendations”

– Long COVID is a debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

– More than 200 symptoms have been identified, affecting multiple organ systems.

– It is estimated that at least 65 million individuals worldwide have long COVID, and the number of cases is increasing.

– Studies have found the presence of SARS-CoV-2 spike antigen in patients with long COVID, suggesting a persistent reservoir of the virus.

– Long COVID can cause damage to various organ systems, primarily attributed to immune-mediated response and inflammation rather than direct viral infection.

– Neurological impacts include cellular dysregulation, myelin loss, cognitive decline, and tissue damage in brain regions connected to the olfactory cortex.

– Ocular manifestations of long COVID include corneal nerve fiber loss, altered pupillary light responses, impaired retinal microcirculation, and retinal abnormalities.

– Long COVID may be comorbid with conditions such as Ehlers–Danlos syndrome, hypermobility, neuro-orthopaedic spinal and skull conditions, and endometriosis.

– Reproductive system impacts include menstrual alterations and triggers of long COVID symptoms.

– Various treatments have been suggested for specific symptoms and biological mechanisms associated with long COVID, including pacing, pharmacological interventions, cognitive therapy, and supplements.

– Misinformation, biases, and delays in recognizing non-respiratory sequelae of COVID-19 have affected research and clinical care for long COVID.

– Education, public awareness campaigns, policies, funding, and research efforts are needed to address long COVID and provide adequate care and support.

Key Takeaway:

Long COVID is a complex and widespread illness with a broad range of symptoms and organ system involvement. It can have long-term consequences and requires further research, improved diagnostic and treatment options, and comprehensive support for individuals affected by the condition. Education, public awareness campaigns, and funding are crucial to address the challenges associated with long COVID and ensure better care for affected individuals.

Interactions between Symptoms and Psychological Status in Irritable Bowel Syndrome: Exploratory Study of Probiotic Combination

Groeger D, Murphy EF, Tan HT, Larsen IS, O’Neill I, Quigley EM. Interactions between symptoms and psychological status in irritable bowel syndrome: An exploratory study of the impact of a probiotic combination. Neurogastroenterol Motil. 2023;35(1):e14477. doi:10.1111/nmo.14477

**Title: Interactions between Symptoms and Psychological Status in Irritable Bowel Syndrome: Exploratory Study of Probiotic Combination**

– Stress is known to exacerbate symptoms of irritable bowel syndrome (IBS), and anxiety and depression are commonly associated with IBS.

– Bifidobacterium longum strains 1714® and 35642® have shown positive effects on stress responses and IBS symptoms, respectively.

– The study explores the relationship between the psychological and visceral effects of the two strains (COMBO) in IBS subjects and biomarkers of stress and inflammation.

– Participants were categorized into low stress and moderate stress groups based on perceived stress scale scores and anxiety/depression levels.

– Oral administration of the COMBO product to moderate/severe IBS patients increased cortisol awakening response (CAR) at Week 4 but returned to baseline levels by Week 8 post-treatment.

– Female IBS patients had higher baseline morning salivary cortisol levels and a blunted CAR compared to non-IBS stress controls.

– The combination of B. longum strains normalized CAR and improved IBS symptoms and stress response, but the effects diminished in the washout period.

– Symptom severity correlated with depression levels but not anxiety or sleep quality.

– The combination of strains reduced anxiety and depression levels, improved sleep quality and visceral perception, and these improvements persisted for 8 weeks after treatment.

– TNF-α levels were decreased after treatment, correlating with improvements in depression, sleep quality, anxiety, and IBS symptoms.

– Increases in plasma levels of the neurotrophin BDNF were observed after treatment.

– The study provides valuable information on the efficacy and interaction of the two strains, estimating the carryover effect and washout period.

– Different mechanisms may underpin IBS symptoms, stress response, and comorbid anxiety and depression.

– The findings may not be applicable to IBS patients without comorbid anxiety and depression.

Key Takeaway:

This exploratory study highlights the interactions between symptoms and psychological status in irritable bowel syndrome (IBS) and the impact of a probiotic combination. The combination of Bifidobacterium longum strains 1714® and 35642® showed positive effects on stress responses, IBS symptoms, and psychological distress in IBS patients with comorbid anxiety and depression. The study suggests that different mechanisms may contribute to IBS symptoms and comorbid conditions, emphasizing the importance of considering psychological factors in IBS management.