ISSN: 2455-2283
Archives of Clinical Gastroenterology
Research Article       Open Access      Peer-Reviewed

Intestinal dysbiosis: definition, clinical implications, and proposed treatment protocol (Perrotta Protocol for Clinical Management of Intestinal Dysbiosis, PID) for the management and resolution of persistent or chronic dysbiosis

Giulio Perrotta*

Psychologist sp.ing in Strategic Psychotherapy, Forensic Criminologist, Legal Advisor sp.ed SSPL, Researcher, Essayist, Institute for the study of psychotherapies - ISP, Via San Martino della Battaglia no. 31, 00185, Rome, Italy
*Corresponding author: Dr. Giulio Perrotta, Psychologist sp.ing in Strategic Psychotherapy, Forensic Criminologist, Legal Advisor sp.ed SSPL, Researcher, Essayist, Institute for the study of psychotherapies - ISP, Via San Martino della Battaglia no. 31, 00185, Rome, Italy, E-mail: info@giulioperrotta.com
Received: 05 July, 2021 | Accepted: 23 July, 2021 | Published: 26 June, 2021

Cite this as

Perrotta G (2021) Intestinal dysbiosis: definition, clinical implications, and proposed treatment protocol (Perrotta Protocol for Clinical Management of Intestinal Dysbiosis, PID) for the management and resolution of persistent or chronic dysbiosis. Arch Clin Gastroenterol 7(2): 056-063. DOI: 10.17352/2455-2283.000100

The human intestinal Microbiota is considered the second brain, because of its implications and correlations in hundreds of functional and dysfunctional processes. Therefore, if knowing the Microbiome (and the Microbiota) is important from a neurobioimmunological point of view, on the other hand it is equally important to investigate the correlations between dysbiosis and the onset of specific physical and psychological diseases. This study focuses on the scientific literature on natural and integrative treatments for intestinal dysbiosis, in order to identify a protocol that has the lowest possible risk and the best possible results, both in the acute phase (for the resolution of symptoms or as a preventive function) and in the chronic phase (for the management of the morbid condition and its clinical consequences).

Contents of the manuscript

Introduction

The term “intestinal microbiota” refers to the set of symbiotic microorganisms (bacteria, viruses, mycetes and protozoa) found in the human digestive tract, and is formed by different ecological niches that host a population consisting of a plurality of species and many strains; from the term “microbiota” we can distinguish the term “microbiome” which is used to refer to the totality of the genetic heritage that the microbiota is able to express. It is no coincidence that the “microbiota” is considered a real “organ within the organ” as it performs functions that we would otherwise not be able to perform, including the ability to assimilate indigestible components of our diet, such as plant polysaccharides. The intestinal mucosa, after the respiratory one, represents the largest surface of our organism: a real defense organ that acts as a barrier against immunogenic or harmful factors present in the intestinal lumen. In fact, we coexist with many different species of bacteria; in particular, in humans there are up to a thousand different species of microorganisms (of which four hundred are just bacteria). However, the types of bacteria are different depending on the portion of the gastrointestinal tract taken into consideration, since in the stomach Helicobacter Pylori prevails, while in the intestine (from ileum to colon) the bacterial species are much greater and variable. Components of the human microbiota include those that cause fermentation (80%) such as Lactobacillus and Bifidobacteria, and those that instead cause putrefaction of the remains (20%) such as Escherichia, Bacteroides, Eubacteria and Clostridium. Many are useful and harmless as constituents of the human microbiota in eubiotic equilibrium, but taken individually they can be dangerous or even deadly. Generally, these bacteria are divided into: a) commensal or physiological, which belong to the organism; b) pathogenic, which cause a disease); c) probiotic, which influence the host by improving the intestinal microbial balance. Equally important in the field of Microbiota are prebiotics, i.e. non-digestible food ingredients that in the large intestine stimulate the growth/metabolic activity of a limited number of microbial groups, important for a good functioning of the organism and symbiotics that are a combination of probiotics and prebiotics [1].

Intestinal homeostasis and intestinal dysbiosis

The intestinal homeostasis (or eubiosis), is “the natural tendency to achieve a relative stability, both of internal chemical-physical properties and behavioral, which is common to all living organisms, for which this dynamic regime must be maintained over time, even when external conditions vary, through precise self-regulatory mechanisms”. The purpose of the intestinal microbiota is to maintain this balance, as it regulates the integrity of the epithelium, the motility of the intestine (peristalsis) and the formation of the immune system (innate and adaptive immune responses). The immune system, in the maintenance of intestinal homeostasis is called into play for the presence of good and bad luminal bacteria, food antigens, so it is continuously stimulated [1,2].

In homeostasis (condition of balance), therefore, the microbiota performs efficiently and effectively; on the contrary, in the hypothesis of “dysbiosis”, which is a perturbation of the normal homeostatic balance, the intestine loses its natural permeability and the organism falls ill more easily, firstly going through a series of acute and temporary imbalances, such as colitis, diarrhea, constipation and digestive disorders, up to a whole series (if the dysbiotic cause should persist) of digestive disorders, constipation and digestive disorders, up to a whole series (if the dysbiotic cause should persist or become chronic) of chronic Inflammatory Bowel Diseases (IBD or MICI), including Crohn’s disease and ulcerative colitis and necrotizing enterocolitis in premature infants [1,3].

In addition to chronic inflammatory diseases, directly caused and fed by the intestinal dysbiotic state, recent studies have shown a direct correlation between dysbiosis and other extraintestinal pathologies, including diabetes, atherosclerosis, metabolic syndrome, autoimmune and neurodegenerative diseases, cardiac and circulatory disorders, atopic dermatitis, psoriasis, asthma and food allergies and intolerances [1,4-19]. But also other conditions, at first unlikely hypothesis, are actually directly correlated with intestinal dysbiosis, to the point of being concauses or even elements favoring or aggravating the pathology itself: we are talking about autism [20-31], epilepsy [32-36], sleep disorders [37-38], neurodegenerative diseases [39-43], eating disorders [44-45] and obesity [46], psychotic disorders [47-52], bipolarity [53-55] and personality disorders [56-64]. The correlation between gut dysbiosis and severe forms of Covid-19 has also recently been demonstrated [65-68].

The target of clinical treatment must therefore be the “intestinal dysbiosis” [1,69,70], in order to promote a new homeostasis (eubiosis). In the clinic, four forms of dysbiosis are recognized, each of them with a precise etiopathological and symptomatic mechanism, caused in any case by a reduction in the diversity of bacterial species, reduction of beneficial species and/or proliferation (increase) of harmful species [1]:

“putrefactive”, which originate from an increase in the share of Bacteroides at the expense of Bifidobacteria, is caused by an excessive intake of meat and saturated fats associated with a poor introduction of insoluble vegetable fibers.

“fermentative”, which originate from a poor acid secretion by the stomach associated with an overproduction of bacteria and yeasts in the stomach and small intestine, often motivated by an intolerance to gluten and carbohydrates.

“deficiency” and “sensitization”, often difficult to differentiate between them. Both forms are caused and maintained by excessive intake of toxic pollutants, antibiotic therapies and more generally by conditions that cause a decrease in the quotas of probiotic bacteria and an alteration of intestinal motility.

Dietary and integrative treatment for the management of intestinal dysbiosis: Proposed protocol (Perrotta Protocol for the clinical management of intestinal dysbiosis, PGD)

In the literature, dozens of studies have focused on the search for one or more elements that can help the intestine to regain its natural eubiosis, without ever taking into account the holistic and omnidimensional approach related to both nutritional intake and individual nutrients; in essence, the studies are always focused on the introduction of the element deficient or the element that can improve the intestinal eubiosis without ever focusing on the overall picture and the rules of management of the patient as a whole.

Thus, what follows is the result of the literature search to meet this need [71-102]. Specifically, the proposed protocol consists of four different steps:

a) Complete patient history: Prepare a specific personal and family history to identify acute and chronic causes and symptomatology, and then proceed to a targeted and personalized treatment plan, using the specific questionnaire on the protocol model under review (PID-Q).

b) Arrangements for serum and instrumental check-up: The patient is invited to undergo the following analyses before starting the new dietary and integrative regimen:

a) Baseline serum tests: CBC with leukocyte formula, erythrocyte sedimentation rate, thrombin, prothrombin, homocysteine, blood glucose, blood glucose curve, amylase, lipase, gamma glutamyltranspeptidase, cholesterol, triglycerides, bilirubin, creatinine, uric acid, nitrogen, thyrotropin, protein electrophoresis, total immunoglobulins A-E-G-M, sodium, potassium, magnesium, iron, ferritin, vitamin b6, vitamin b12, vitamin d3.

b) Specific serum analyses: to be evaluated based on patient history.

c) Urinary analyses: urinary chemistry-physical, e-GFR (24h).

d) Complete echo-abdomen;

e) Identification sequencing of intestinal microbial communities.

Preparation of a personalized and individualized food plan that takes into account the specific allergies/intolerances of the patient. This plan [71-74] includes

a) a balanced caloric regimen, according to the weight and age of the patient, rich in fiber (20-25 gr/dié), cereals (50 gr/dié), fruit (200-300 gr/dié), vegetable oils (e.g., extra virgin olive oil) and vegetables (600-1000 gr/dié), with abstention from the intake of sugars (simple) and/or carbohydrates (complex sugars) after 5 pm;

b) water intake between 2000 ml / dié and 2500 ml / dié, of which at least 75% of natural mineral water;

c) absolute abstention from the intake of the following foods packaged products (sweet and salty) and sausages of animal origin (ham, mortadella, speck, ...), products stored in aluminum or plastic cans, gluten-based or contaminated products (bread, pasta and flours), yeast (you can replace it with bicarbonate for natural leavening), sugar, salt, butter and products with a high lipid value, products cooked on the grill or burning the surface, narcotics, cigarettes and cigars;

d) mild abstention (maximum 3 times a week) from the intake of the following foods: meat of animal origin (of which 2 times white meat and 1 time red meat), potatoes, tomatoes, eggplant, peppers, zucchini, cow’s milk and derivatives (cheese made from cow’s milk), products with moderate lipid value, alcohol (wine and beer, moderate amounts);

e) moderate abstention (maximum 1 time per week) from the intake of the following foods: hard liquor (limited quantities) and products cooked in fried mode,

f) brisk walking for 40-60 minutes, for a total of about 5000 steps/day, 3 times a week, every other day.

Administration of the supplemental regimen

A basic kit is prepared to be taken daily (unless otherwise specified) and composed of the following elements:

✓ Prebiotic elements (e.g., inulin and fructooligosaccharides) [77,79] and Probiotics [74,75,77,79,94,95], based on individual history, symptom severity, and type of dysbiosis encountered, administered in the indicative amount of 10-30 billion ferments/day. Particular attention to Bifidobacteria [76] and Lactobacilli [96-98] (including Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum, Bacillus subtilis, Streptococcus thermophilus, Enterococcus faecium, Lactobacillus gasseri, Lactobacillus casei, Lactobacillus rhamnosus).

✓ Omega 3 (alpha-linoleic acid), 6 (oleic acid), and 9 (linoleic acid), administered in the amount of 1000-2000 mg/dié [78].

✓ Vitamin A (Retinol), administered in the amount of 1 mg/dié [80-82, 89]

✓ Vitamin B1 (Thiamine), administered in the amount of 1 mg/dié [83]

✓ Vitamin B2 (Riboflavin), administered in the amount of 0.5 mg/dié per 1000 Kcal introduced in the diet [83]

✓ Vitamin B3 (Niacin or PP), administered in the amount of 15 mg/dié [83]

✓ Vitamin B5 (Pantothenic Acid), administered in the amount of 5 mg/dié [83]

✓ Vitamin B6 (Pyridoxine), administered in the amount of 1 mg/dié [83]

✓ Vitamin B7 (Inositol), administered in the amount of 500 mg/dié [83]

✓ Vitamin B8 (Biotin), administered in the amount of 100 mg/dié [83].

✓ Vitamin B9 (Folic acid), administered in the amount of 2 mg/dié [84].

✓ Vitamin B12 (Cobalamin), administered in the amount of 1000 mg/dié [85].

✓ Vitamin C, administered in the amount of 1000-3000 mg/dié [86,87].

✓ Vitamin D3, administered in the amount of 1000-4000 IU/dié (5 days/week) + Vitamin K, administered in the amount of 1000-2000 mcg/dié (the suggested dose should be between 500 and 1000 mcg but the antagonistic efficacy of Coenzyme q10 in the protocol must be taken into account). Vitamin D3 and vitamin K may not be necessary if serum indicates this [81,85,88,89].

✓ Vitamin E, administered in the amount of 1000-2000 mg/dié [90]

✓ Curcudine, administered in the amount of 200-500 mg/dié + Piperine, administered in the amount of 5 mg or Bromelain, administered in the amount of 200 mg/dié [91]

✓ Quercitin, administered in the amount of 200-500 mg/dié [91]

✓ Lactoferrin, administered in the amount of 300-500 mg/dié [92]

✓ Coenzyme q10, administered in the amount of 100 mg/dié [93]

✓ Sodium Butyrate, administered at a dose of 1000-2000 mg/dié [103-105]

✓ Glutathione, administered at a dose of 500-1000 mg/dié [106].

These doses are evaluated according to a hypothetical proposal profile, based on analytical and empirical evidence from previous studies, which indicate certain thresholds of administration depending on the objectives to be achieved. Clearly, the protocol is here a proposal and therefore during future experiments it may be subject to change Table 1.

Perrotta intestinal dysbiosis clinical management protocol – Questionnaire, PID-Q

Associated with the proposed protocol, this research work also uses a specific questionnaire: Perrotta Intestinal Dysbiosis Clinical Management Protocol - Questionnaire, PID-Q.

This questionnaire is specifically structured in 4 parts in order to have all the information needed to monitor the sample population holistically:

1) Section A contains the personal and contact information of each individual patient.

2) Section B contains the medical history of each individual patient, with particular attention to the following profiles: medical conditions during gestation, childhood and throughout development, with distinction between physical and psychological symptoms; previous and current drug therapy; specific allergies and any therapy used.

3) Section C contains anamnestic family data, of relatives and relatives-in-law of first and second degree, in such a way as to be able to reconstruct any family or hereditary conditions.

4) Section D represents the diary of the protocol, with the list of specific activities in the phase preceding the beginning of the protocol until the concluding phases, subdivided by therapies, diet and reference notes, weekly and then monthly, until the duration of the entire semester.

Appendix no. 1: Perrotta, Intestinal Dysbiosis Clinical Management Protocol - Questionnaire, PID-Q).

Concluding considerations

The application of this proposal as an experiment could bring very interesting results, in the light of scientific literature, both in the acute phase (for the resolution of symptoms or as a preventive function) and in the chronic phase (for the management of the morbid condition and its clinical consequences). Awaiting further developments, we await new research able to identify the exact distribution of all microorganisms that are part of the microbiota and the complete mapping of the microbiome.

Appendix

  1. Perrotta G (2021) The intestinal microbiota: towards a multifactorial integrative model. Eubiosis and dysbiosis in morbid physical and psychological conditions. Arch Clin Gastroenterol 7: 024-035. Link: https://bit.ly/3BEZA9c
  2. Belkaid Y, Hand T (2014) Role of the Microbiota in Immunity and inflammation. Cell 157: 121-141. Link: https://bit.ly/3vR2c0k
  3. Graziani C, Talocco C, De Sire R, Petito V, Lopetuso LR, et al. (2019) Intestinal permeability in physiological and pathological condictions: major determinants and assessment modalities. Eur Rev Med Pharm Sci 23: 795-810. Link: https://bit.ly/3wMhvHP
  4. Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, et al. (2018) Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastro 11: 1-10. Link: https://bit.ly/34xGMtp
  5. Eslami M, Bahar, M. Hemati, Z. Rasouli Nejad, F. Mehranfar, et al. (2021) Dietary pattern, colonic microbiota and immunometabolism interaction: new frontiers for diabetes mellitus and related disorders. Diabet Med 38: e14415. Link: https://bit.ly/2SHvQqk
  6. Fatkhullina AR, Peshkova IO, Dzutsev A, Aghayev T, McCulloch JA, et al. (2018) An Interleukin-23-Interleukin-22 Axis regulates intestinal microbial homeostasis to protect from diet-induced atherosclerosis. Immunity 49: 943-957. Link: https://bit.ly/3uG8Bu5
  7. Torres N, Guevara-Cruz M, Velázquez-Villegas LA, Tovar AR (2015) Nutrition and Atherosclerosis. Arch Med Res 46: 408-426. Link: https://bit.ly/3fWiLS1
  8. Petukhov VA, Karalkin AV, Ibragimov TI, Petukhova NA, Briushkov AIu, et al. (2001) Disturbance of liver functions and dysbiosis in patients with lipid distress syndrome and its treatment with lactulose preparation “Duphalac”. Ross Gastro Zh 92-102. Link: https://bit.ly/3fzYuCS
  9. Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquín AJ, Pizano-Zárate ML (2017) Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J Imm Res 2017: 4835189. Link: https://bit.ly/2SOCbR2
  10. De Luca F, Shoenfeld Y (2019) The microbiome in autoimmune diseases. Clin Exp Immunol 195: 74-85. Link: https://bit.ly/2R7AvkS
  11. Kigerl AK, Hall JC, Wang L, Mo X, Yu Z, et al. (2016) Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med 213: 2603-2620. Link: https://bit.ly/3c5nMGA
  12. Van IJzendoorn SCD, Derkinderen P (2019) The Intestinal Barrier in Parkinson's Disease: Current State of Knowledge. J Parkinsons Dis 9(s2):S323-S329. Link: https://bit.ly/2R9PryZ
  13. Janeiro MH, Ramírez MJ, Solas M (2021) Dysbiosis and Alzheimer's Disease: Cause or Treatment Opportunity? Cell Mol Neurobiol. Link: https://bit.ly/3p7uwsU
  14. Tang WHW, Kitai T, Hazen SL (2017) Gut Microbiota in Cardiovascular Health and Disease. Circ Res 120: 1183-1196. Link: https://bit.ly/3rxCM6E
  15. Lacour JP (2015) Skin microbiota and atopic dermatitis: toward new therapeutic options? Ann Derm Ven 142: 1: S18- S22. Link: https://bit.ly/3yPsEcJ
  16. Myers B, Brownstone N, Reddy V, Chan S, Thibodeaux Q, et al. (2020) The gut microbiome in psoriasis and psoriatic arthritis, Best Pract Res Clin Rheu 33: 101494. Link: https://bit.ly/2UKNzyo
  17. Chunxi L, Haiyue L, Yanxia L, Jianbing P, Jin S, et al. (2020) The gut microbiota and respiratory diseases: new evidence. J Imm Res 2020: 2340670. Link: https://bit.ly/3vAthVA
  18. Zhao W, Ho HE, Bunyavanich S (2019) The gut microbiome in food allergy. Ann All Asthma Imm 122: 276-282. Link: https://bit.ly/3kW3Xai
  19. Schink M, Konturek PC, Tietz E, Dieterich W, Pinzer TC, et al. (2018) Microbial patterns in patients with histamine intolerance. J Phy Pharm 69. Link: https://bit.ly/3fX2Gvi
  20. Wasilewska J, Jarocka-Cyrta E, Kaczmarski M (2009) Gastrointestinal abnormalities in children with autism. Pol Mer Lek 27: 40-43. Link: https://bit.ly/3BHJV9p
  21. Fattorusso A, Di Genova L, Dell'Isola GB, Mencaroni E, Esposito S (2019) Autism spectrum disorders and the gut microbiota. Nutrients 11: 521. Link: https://bit.ly/34CVdfA
  22. Srikantha P, Mohajeri MH (2019) The possible role of the Microbiota-Gut-Brain-Axis in Autism spectrum disorder. Int J Mol Sci 20: 2115. Link: https://bit.ly/3i7tpIc
  23. Perrotta G (2019) Autism Spectrum Disorder: Definition, contexts, neural correlates and clinical strategies. J Neurol Neurother 4: 136. Link: https://bit.ly/36UNF9b
  24.  Heather K, Rose D, Ashwood P (2018) The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders. Curr Neurol Neurosci Rep 18: 81. Link: https://bit.ly/3yTEl2g
  25. Yang Y, Tian J, Yang B (2018) Targeting gut microbiome: A novel and potential therapy for autism. Life Sci 194: 111–119. Link: https://bit.ly/3uCFDvb
  26. Li Q, Han Y, Dy ABC, Hagerman RJ (2017) The Gut Microbiota and Autism Spectrum Disorders. Front Cell Neurosci 11: 120. Link: Link: https://bit.ly/3vGRVDU
  27. Ding HT, Taur Y, Walkup JT (2017) Gut Microbiota and Autism: Key Concepts and Findings. J Autism Dev Disord 47: 480-489. Link: https://bit.ly/2TFPJiw
  28. Berding K, Donovan SM (2016) Microbiome and nutrition in autism spectrum disorder: current knowledge and research needs. Nutr Rev 74: 723-736. Link: https://bit.ly/2WlEm07
  29. Mead J, Ashwood P (2015) Evidence supporting an altered immune response in ASD. Immunol Lett 163: 49-55. Link: https://bit.ly/2Van5qb
  30. Song Y, Liu C, Finegold SM (2004) Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ MicroM 70: 6459-6465. Link: https://bit.ly/3iLKaYi
  31. Parracho HM, Bingham MO, Gibson GR, McCartney AL (2005) Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 54: 987-991. Link: https://bit.ly/3p8JVcy
  32. Iannone LF, Gómez-Eguílaz M, Citaro R, Russo E (2020) The potential role of interventions impacting on gut-microbiota in epilepsy, Expert Rev Clin Pharma 13: 423-435. Link: https://bit.ly/34zPpn7
  33. Lum GR, Olson CA, Hsiao EY (2020) Emerging roles for the intestinal microbiome in epilepsy. Neurobiol Dis 135: 104576. Link: https://bit.ly/3fXlSt0
  34. Huang C, Li X, Wu L, Wu G, Wang P, et al. (2021) The effect of different dietary structure on gastrointestinal dysfunction in children with cerebral palsy and epilepsy based on gut microbiota. Brain Dev 43: 192-199. Link: https://bit.ly/2Vanj0v
  35. Perrotta G (2020) Epilepsy: from pediatric to adulthood. Definition, classifications, neurobiological profiles and clinical treatments. J Neurol Neurol Sci Disord 6: 014-029. Link: https://bit.ly/3vz3ltv
  36. Perrotta G (2020) The pharmacological treatment of epileptic seizures in children and adults: introduction, clinical contexts, psychopharmacological profiles and prospects in the neurogenetic field. Journal of Neuroscience and Neurological Surgery 6. Link: https://bit.ly/3g3hRmV
  37.  Matenchuk BA, Mandhane PJ, Kozyrskyj AL (2020) Sleep, circadian rhythm, and gut microbiota. Sleep Med Rev 53: 101430. Link: https://bit.ly/3x5PNFC
  38. Perrotta G (2019) Sleep-wake disorders: Definition, contexts and neural correlations. J Neurol Psychol 7: 09. Link: https://bit.ly/3hoBiGO
  39.  Spielman LJ, Gibson DL, Klegeris A (2018) Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases. Neurochem Int 120: 149-163. Link: https://bit.ly/3i3DMgl
  40. Perez-Pardo P, Dodiya HB, Engen PA, Naqib A, Forsyth CB, et al. (2018) Gut bacterial composition in a mouse model of Parkinson's disease. Benef Microbes 9: 799-814. Link: https://bit.ly/34yqd0a
  41. Bastiaanssen TFS, Cowan CSM, Claesson MJ, Dinan TG, Cryan JF (2018) Making Sense of… the Microbiome in Psychiatry. Int J Neuropsychopharmacol 22: 37-52. Link: https://bit.ly/3y4UXTX
  42. Riaz Rajoka MS, Zhao H, Li N, Lu Y, Lian Z, et al. (2018) Origination, change, and modulation of geriatric disease-related gut microbiota during life. Appl Microbiol Biotechnol 102: 8275-8289. Link: https://bit.ly/3iJYYql
  43. Gerhardt S, Mohajeri MH (2018) Changes of Colonic Bacterial Composition in Parkinson's Disease and Other Neurodegenerative Diseases. Nutrients 10. pii: E708. Link: https://bit.ly/3yi0uq0
  44. Roubalovà R, Procházková P, Papežová H, Smitka K, Bilej M, et al. (2020) Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin Nutr 39: 676-684. Link: https://bit.ly/2RdmrXg
  45. Perrotta G (2019) Neural correlates in eating disorders: Definition, contexts and clinical strategies. J Pub Health Catalog 2: 137-148. Link: https://bit.ly/3mWmf8s
  46. Fontané L, Benaiges D, Goday A, Llauradó G, Pedro-Botet J (2018) Influence of the microbiota and probiotics in obesity. Clin Invest Arter 30: 271-279. Link: https://bit.ly/36Y4NL9
  47. Dickerson F, Severance E, Yolken R (2017) The microbiome, immunity, and schizophrenia and bipola disorder. Brain Behav Imm 62: 46-52. Link: https://bit.ly/3wNsukw
  48. Gondalia S, Parkinson L, Stough C, Scholey A (2019) Gut microbiota and bipolar disorder: a review of mechanisms and potential targets for adjunctive therapy. Psychoph (Berl) 236: 1433-1443. Link: https://bit.ly/2SHv4tq
  49. Perrotta G (2019) Delusions, paranoia and hallucinations: definitions, differences, clinical contexts and therapeutic approaches. Cientific Journal of Neurology (CJNE) 1: 22-28. Link: https://bit.ly/3ht2nKz
  50. Perrotta G (2020) Dysfunctional sexual behaviors: definition, clinical contexts, neurobiological profiles and treatments. Int J Sex Reprod Health Care 3: 061-069. Link: https://bit.ly/3ryTgKU
  51. Perrotta G (2020) Psychotic spectrum disorders: definitions, classifications, neural correlates and clinical profiles. Ann Psychiatry Treatm 4: 070-084. Link: https://bit.ly/2QI9kNc
  52. Mencacci C, Salvi V (2020) Microbiota e psicosi, Microbioma Microbiota, 2/2020.
  53. Meyyappan AC, Forth E, Wallace CJK, Milev R (2020) Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry 20: 299. Link: https://bit.ly/3wNDyhg
  54. Cenit MC, Sanz Y, Codoñer-Franch P (2017) Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol 23: 5486-5498. Link: https://bit.ly/3zArcKZ
  55. Perrotta G (2019) Bipolar disorder: definition, differential diagnosis, clinical contexts and therapeutic approaches. J Neuroscience and Neurological Surgery 5. Link: https://bit.ly/3hKPdqM
  56. Kim HN, Yun Y, Ryu S, Chang Y, Kwon MJ, et al (2018) Correlation between gut microbiota and personality in adults: a cross-sectional study. Brain Beh Imm 69: 374-485. Link: https://bit.ly/2R7A3Dc
  57. Bauer ME, Teixeira AL (2018) Inflammation in psychiatric disorders: what comes first? Ann N Y Acad Sci 1437: 57-67. Link: https://bit.ly/34CUZVM
  58. Kennedy PJ, Murphy AB, Cryan JF, Ross PR, Dinan TG, et al. (2016) Microbiome in brain function and mental health. Trends Food Science & Technology 57: 289-301. Link: https://bit.ly/3iLg1YX
  59. Perrotta G (2020) Borderline Personality Disorder: definition, differential diagnosis, clinical contexts and therapeutic approaches. Ann Psychiatry Treatm 4: 043-056. Link: https://bit.ly/3hx2B1N
  60. Perrotta G (2020) Narcissism and psychopathological profiles: definitions, clinical contexts, neurobiological aspects and clinical treatments. J Clin Cases Rep 4: 12-25. Link: https://bit.ly/2X8wzzF
  61. Perrotta G (2021) Histrionic personality disorder: Definition, clinical profiles, differential diagnosis and therapeutic framework. Arch Community Med Public Health 7: 001-005. Link: https://bit.ly/3cuga0H
  62. Perrotta G (2021) The state of consciousness: from perceptual alterations to dissociative forms. Defining, neurobiological and clinical profiles. J Neuro Neurol Sci Disord 7: 006-018. Link: https://bit.ly/2P9JVvf
  63. Perrotta G (2021) Avoidant personality disorder: Definition, clinical and neurobiological profiles, differential diagnosis and therapeutic framework. J Neuro Neurol Sci Disord 7: 001-005. Link: https://bit.ly/3p5S9SP
  64. Settani CR, Ianiro G, Bibbò S, Cammarota G, Gasbarrini A (2021) Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation. Prog Neuropsychopharmacol Biol Psychiatry 109: 110258. Link: https://bit.ly/3fWwzfn
  65. Perrotta G (2021) The psychological and immunobiological implications of Covid-19: the possible correlation with previous pandemics and the suggestive therapeutic hypothesis of convalescent plasma. Glob J Clin Virol 6: 007-011. Link: https://bit.ly/3fWi8b7
  66. Scaldaferri F, Ianiro G, Privitera G, Lopetuso LR, Vetrone LM, et al. (2020) The Thrilling Journey of SARS-CoV-2 into the Intestine: From Pathogenesis to Future Clinical Implications. Inflamm Bowel Dis 26: 1306-1314. Link: https://bit.ly/3p5rQMy
  67. Ferreira C, Viana SD, Reis F (2020) Is Gut Microbiota Dysbiosis a predictor of increased susceptibility to poor outcome of Covid-19 patients? An update. Microorganisms 9: 53. Link: https://bit.ly/3x5yPr1
  68. Perrotta G (2021) Covid-19 pandemic: all possible effective solutions to eradicate the problem. Cross-sectional analysis of clinical, socioeconomic, political and psychological profile. Arch Community Med Public Health 7: 099-110. Link: https://bit.ly/3BxkNSI
  69. Iebba V (2018) Il microbiota. Un nuovo mondo inesplorato. Carocci Ed, Roma.
  70. Ottman N, Smidt H, de Vos WM, Belzer C (2012) The function of our microbiota: who is out there and what do they do?. Front Cell Infect Microbiol 2: 104. Link: https://bit.ly/2WjWojk
  71. Meng X, Zhang G, Cao H, Yu D, Fang X, et al. (2020) Gut dysbacteriosis and intestinal disease: mechanism and treatment. J Appl Microbiol 129: 787-805. Link: https://bit.ly/3y5pdOz
  72. Saffouri GB, Shields-Cutler RR, Chen J, Yang Y, Lekatz HR, et al. (2019) Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nat Commun 10: 2012. Link: https://go.nature.com/2VggRFi
  73. Candido TLN, Bressan J, Alfenas RCG (2018) Dysbiosis and metabolic endotoxemia induced by high-fat diet. Nutr Hosp 35: 1432-1440. Link: https://bit.ly/3kTGRAO
  74. Ghibbar R, Dieleman AL (2019) The Gut Microbiota in Celiac Disease and probiotics. Nutrients 11: 2375. Link: https://bit.ly/3kUXSKV
  75. Seon-Kyun K, Guevarra RB, Kim YT, Kwon J, Kim H, et al. (2019) Role of Probiotics in Human Gut Microbiome-Associated Diseases. J Microbiol Biotechnol 29: 1335-1340. Link: https://bit.ly/2VdIlLG
  76. Tojo R, Suárez A, Clemente MG, de los Reyes-Gavilán CG, Margolles A, et al. (2014) Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol 20: 15163-76. Link: https://bit.ly/3zD8K4a
  77. Tsai YL, Lin TL, Chang CJ, Wu TR, Lai WF, et al. (2019) Probiotics, prebiotics and amelioration of diseases. J Biomed Sci 26: 3. Link: https://bit.ly/3BF1qH8
  78. Costantini L, Molinari R, Farinon B, Merendino N (2017) Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int J Mol Sci 18: 2645. Link: https://bit.ly/3i1A5Y4
  79. Gagliardi A, Totino V, Cacciotti F, Iebba V, Neroni B, et al. (2018) Rebuilding the Gut Microbiota Ecosystem. Int J Environ Res Public Health 15: 1679. Link: https://bit.ly/2V5yM1b
  80. Liu J, Liu X, Xiong XQ, Yang T, Cui T et al. (2017) Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders - a pilot study. BMC Microbiol 17: 204. Link: https://bit.ly/3y4UwZz
  81. Cantorna MT, Snyder L, Arora J (2019) Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit Rev Biochem Mol Biol 54: 184-192. Link: https://bit.ly/3iSR3aq
  82. Sirisinha S (2015) The pleiotropic role of vitamin A in regulating mucosal immunity. Asian Pac J Allergy Immunol 33: 71-89. Link: https://bit.ly/36ZK89B
  83. Li Y, Luo ZY, Hu YY, Bi YW, Yang JM, et al. (2020) The gut microbiota regulates autism-like behavior by mediating vitamin B 6 homeostasis in EphB6-deficient mice. Microbiome 8: 120. Link: https://bit.ly/3i2RDTu
  84. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, et al. (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol 24: 160-168. Link: https://bit.ly/3eUt9tV
  85. Jiang S, Zhu Q, Mai M, Yang W, Du G (2020) Vitamin B and vitamin D as modulators of gut microbiota in overweight individuals. Int J Food Sci Nutr 71: 1001-1009. Link: https://bit.ly/3x9ubIt
  86. Ratajczak AE, Szymczak-Tomczak A, Skrzypczak-Zielińska M, Rychter AM, Zawada A, et al. (2020) Vitamin C Deficiency and the Risk of Osteoporosis in Patients with an Inflammatory Bowel Disease. Nutrients 12: 2263. Link: https://bit.ly/3rAdo0e
  87. Ikeda S, Takahashi S, Suzuki N, Hanzawa F, Horio F, et al (2020) Gut Microbiota Is Not Involved in the Induction of Acute Phase Protein Expression Caused by Vitamin C Deficiency. J Nutr Sci Vitaminol (Tokyo) 66: 19-23. Link: https://bit.ly/2WppZYN
  88. Sassi F, Tamone C, D'Amelio P (2018) Vitamin D: Nutrient, hormone and immunomodulator. Nutrients 10: 1656. Link: https://bit.ly/2UPW63h
  89. Riccio P, Rossano R (2018) Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis. Neurotherapeutics 15: 75-91. Link: https://bit.ly/3y5pIIr
  90. Choi Y, Lee S, Kim S, Lee J, Ha J, et al. (2020) Vitamin E (α-tocopherol) consumption influences gut microbiota composition. Int J Food Sci Nutr 71: 221-225. Link: https://bit.ly/372SsFQ
  91. Shabbir U, Rubab M, Daliri EB, Chelliah R, Javed A, et al (2021) Curcumin, Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota. Nutrients 13: 206. Link: https://bit.ly/2VczWYC
  92. Vega-Bautista A, de la Garza M, Carrero JC, Campos-Rodríguez R, Godínez-Victoria M, et al. (2019) The Impact of Lactoferrin on the Growth of Intestinal Inhabitant Bacteria. Int J Mol Sci 20: 4707. Link: https://bit.ly/34zsZm3
  93. Paley EL, Merkulova-Rainon T, Faynboym A, Shestopalov VI, Aksenoff I (2018) Geographical Distribution and Diversity of Gut Microbial NADH:Ubiquinone Oxidoreductase Sequence Associated with Alzheimer's Disease. J Alzheimers Dis 61: 1531-1540. Link: https://bit.ly/3zFcKkZ
  94. Abdellatif B, McVeigh C, Bendriss G, Chaari A (2020) The promising role of probiotics in managing the altered gut in ASD. Int J Mol Sci 21: 4159. Link: https://bit.ly/3eTwtoW
  95. Morkl S, Butler MI, Holl A, Cryan JF, Dinan TG (2020) Probiotics and the Microbiota-Gut-Brain Axis: Focus on Psychiatry. Curr Nutr Rep 9: 171-182. Link: https://bit.ly/3iLMbDQ
  96. Azad MAK, Sarker M, Li T, Yin J (2018) Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int 2018: 9478630. Link: https://bit.ly/3x4PpaC
  97. Tonucci LB, Dos Santos KM, De Luces Fortes Ferreira CL, Ribeiro SM (2017) Gut microbiota and probiotics: Focus on diabetes mellitus. Crit Rev Food Sci Nutr 57: 2296-2309. Link: https://bit.ly/3rzCg8d
  98. Valeriano VDV, Balolong MP, Kang DK (2017) Probiotic roles of Lactobacillus sp. in swine: insights from gut microbiota. J Appl Microbiol 122: 554-567. Link: https://bit.ly/36XPe6k
  99. Durack J, Lynch SV (2018) The gut microbiome: Relationships with disease and opportunities for therapy. J Exp Med 216: 20-40. Link: https://bit.ly/3hZVm4h
  100. Kho ZY, Lal SK (2018) The Human Gut Microbiome - A Potential Controller of Wellness and Disease. Front Microbiol 9: 1835. Link: https://bit.ly/3i4nVgV
  101. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, et al. (2015) Role of the normal gut microbiota. World J Gastroenterol 21: 8787–8803. Link: https://bit.ly/3uEgWhY
  102. Kamada N, Chen GY, Inohara N, Núñez G (2013) Control of Pathogens and Pathobionts by the Gut Microbiota. Nat Immunol 14: 685-690. Link: https://bit.ly/3xbetwQ
  103. Zhou D, Pan Q, Xin FZ, Zhang RN, He CX, et al. (2017) Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota. World J Gastroenterol 23: 60-75. Link: https://bit.ly/2WkvIip
  104. Fang W, Xue H, Chen X, Chen K, Ling W (2019) Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice. J Nutr 149: 747-754. Link: https://bit.ly/3iQaK2e
  105. Makizaki Y, Uemoto T, Yokota H, Yamamoto M, Tanaka Y, et al. (2021) Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis. PLoS One 16: e0248584. Link: https://bit.ly/3y6OS9w
  106. Rihua X, Aruhan, Xiu L, Sheng S, Liang Y, et al. (2019) Exopolysaccharides from Lactobacillus buchneri TCP016 Attenuate LPS- and d-GalN-Induced Liver Injury by Modulating the Gut Microbiota. J Agric Food Chem 67: 11627-11637. Link: https://bit.ly/3eWPxCH
© 2021 Perrotta G. This is an open-Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.