Medicinski podmladak

Human microbiome: pathophysiological and clinical aspects

Irena Aranđelović — Mon, 03 Nov 2025 00:00:00 +0100

Trilioni mikroorganizama koji žive u i na telu čoveka, njihovi geni i metaboliti, jednim imenom nazvani humani mikrobiom, danas su prepoznati kao aktivni učesnici u gotovo svakom aspektu ljudske biologije. Ovaj raznovrstan i dinamičan ekosistem funkcioniše poput skrivenog organa i duboko je integrisan u fiziologiju i očuvanje zdravlja čoveka. Tokom poslednje dve decenije humani mikrobiom, nekada pozicioniran u marginalnim sferama istraživanja, postao je centralna tema biomedicinskih nauka. Otkriće da mikrobne zajednice imaju ključnu ulogu ne samo u metabolisanju nutrijenata već i u modulaciji imunskog sistema, neuroendokrinoj komunikaciji i održavanju sistemske homeostaze, značajno je promenilo naše razumevanje zdravlja i bolesti. Koncept mikrobioma kao centralnog aktera u održavanju zdravlja i razvoju bolesti više se ne posmatra kao hipoteza već kao potvrđena naučna realnost koja transformiše savremenu medicinsku praksu.

Microbiota and immune system

Emina Milošević — Tue, 18 Nov 2025 14:04:05 +0100

Čovek predstavlja složen biološki ekosistem koji čine sopstveni organizam i mikrobiom koji ga naseljava. Mikrobiom obuhvata trilione mikroorganizama, uključujući bakterije, viruse, gljive i arhee, zajedno sa njihovim metaboličkim produktima, genima i pripadajućim genskim produktima. Ovaj složeni ekosistem obavlja brojne fiziološki važne funkcije, učestvujući u procesima varenja, sintezi vitamina, zaštiti od patogena i interakciji sa supstancama iz spoljašnje sredine.

Među njegovim najznačajnijim ulogama ističe se doprinos mikrobiote razvoju i sazrevanju imunskog sistema. Odnos između imunskog sistema i mikrobiote izuzetno je višestruk i dvosmeran, pri čemu ostvaruje sistemske efekte koji prevazilaze lokalna tkiva u kojima se te interakcije primarno odvijaju.

Narušavanje ove ravnoteže dovodi do disbioze, stanja koje je povezano sa nastankom različitih inflamatornih i autoimunskih poremećaja. Rasvetljavanje uzajamnih regulatornih mehanizama koji povezuju imunski sistem i mikrobiotu ključno je za razumevanje patofizioloških procesa koji nastaju kada dođe do poremećaja u njihovoj interakciji.

Ovaj pregledni rad ima za cilj da predstavi ulogu mikrobiote u razvoju i fiziološkom funkcionisanju imunskog sistema radi boljeg razumevanja posledica disbalansa unutar ovog odnosa.

Oral microbiome: physiological and pathological impact on oral and systemic health

Milica Jovanović Medojević — Thu, 06 Nov 2025 00:00:00 +0100

Oralni mikrobiom predstavlja kompleksan i dinamičan ekosistem različitih mikrobnih zajednica čija je raznolikost rezultat specifičnih anatomskih i fizioloških uslova usne duplje. Očuvanje ravnoteže mikrobioma, eubioze, od suštinskog je značaja za humano zdravlje. Komensalne vrste sprečavaju kolonizaciju patogena, moduliraju imuni odgovor, učestvuju u održavanju metaboličke homeostaze, te doprinose pravilnom fiziološkom funkcionisanju.

Poremećaj ravnoteže oralnog mikrobioma, disbioza, povezan je sa razvojem oralnih oboljenja poput karijesa, parodontopatije, gingivitisa, kandidijaze i malignih promena ali i sa sistemskim oboljenjima, uključujući kardiovaskularna i respiratorna oboljenja, dijabetes melitus, reumatoidni artritis, komplikacije u trudnoći i neurodegenerativne poremećaje. Takođe, hronična sistemska oboljenja mogu dodatno narušiti mikrobiološku ravnotežu usne duplje, stvarajući začarani krug patoloških promena.

Prevencija disbioze zasniva se na pravilnoj oralnoj higijeni, redovnim stomatološkim kontrolama, uravnoteženoj ishrani sa ograničenim unosom rafinisanih šećera, kontrolisanoj primeni antibiotika i, potencijalno, na probiotskim i prebiotskim terapijskim pristupima. Savremena istraživanja sve više ukazuju na mogućnost personalizovane stomatološke prakse zasnovane na analizi mikrobiomskog profila pacijenta, što bi moglo unaprediti prevenciju i terapiju kako oralnih, tako i sistemskih oboljenja.

The role of gut microbiome modulation in the management of neurodevelopmental disorders: current evidence and future directions

Dragana Protić, Vladimir Nikolić, Maja Stojković — Tue, 11 Nov 2025 00:00:00 +0100

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other cognitive and behavioral impairments, are increasing globally, placing significant burdens on individuals and healthcare systems. Traditional therapeutic strategies, primarily pharmacologic and behavioral, offer limited efficacy and often fail to address the multifactorial etiology of these conditions. Recent advances in microbiome research highlight the gut microbiota as a potential modulator of brain function via the microbiota–gut–brain axis (MGBA). This bidirectional network influences neurodevelopment through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or microbial imbalance, has been consistently reported in individuals with NDDs, particularly in ASD and ADHD, correlating with symptom severity and gastrointestinal comorbidities. Emerging interventions aimed at restoring microbial balance, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation (FMT), and dietary modifications - demonstrate potential in modulating behaviour and cognition. However, the current evidence is limited by small sample sizes, heterogeneous methodologies, and a lack of long-term follow-up. This mini-review synthesizes current findings on the role of gut microbiome modulation in NDDs, evaluates the therapeutic efficacy of microbiome-based interventions, and discusses future directions, including personalized microbiome-targeted strategies and the need for robust randomized controlled trials.

Microbiota and Alzheimer’s disease: toward new clinical approaches

Jelena Djokić, Miroslav Dinić — Wed, 12 Nov 2025 00:00:00 +0100

Alzheimer’s disease (AD) is now viewed as a systemic disorder in which genetics, the gut microbiome and immune dysregulation converge to accelerate amyloid-β (Aβ) and tau pathology. Genetic studies have identified 70 risk loci. APOE ε4 is the strongest AD risk loci, conferring dose-dependent risk through impaired cholesterol trafficking, reduced Aβ clearance and heightened neuroinflammation. Rare mutations in TREM2 and CD33 further illustrate the centrality of microglia-mediated innate immunity. Importantly, peripheral Th17 skewing, neutrophil hyper-activation and loss of regulatory myeloid cells amplify neuroinflammation. Growing evidence links gut dysbiosis to these genetic factors. APOE ε4 carriers show depletion of Short-Chain Fatty Acids (SCFA)-producing taxa (Gemmiger, Roseburia, Faecalibacterium) and enrichment of pro-inflammatory Proteobacteria (Escherichia/Shigella, Morganella). In mice, APOE4-dependent loss of butyrate-producing bacteria lowers colonic and serum SCFA levels and worsens tauopathy, whereas Germ-free housing, early antibiotics and SCFA supplementation rescue pathology. Large meta-analyses correlate Collinsella and Veillonella with higher AD risk, and Eubacterium nodatum and Prevotella 9 with protection. Metabolomic shifts mirror these compositional changes: acetate, propionate and butyrate, as well as trimethylamine N-oxide (TMAO) promote epigenetic regulation, blood–brain-barrier (BBB) integrity and microglial homeostasis, whereas secondary bile acids compromise cognition. The microbial amyloids and lipopolysaccharide can cross-seed Aβ, activate the NLRP3 inflammasome, and breach the blood-brain barrier. Intermittent fasting, ketogenic diets, specific probiotics (Bifidobacterium breve A1, Lacticaseibacillus rhamnosus CBT-LR5), sodium oligomannate (GV-971) or fecal microbiota transplantation can remodel gut ecology, raise beneficial SCFAs, dampen pro-inflammatory cytokines and improve cognition in patients with AD or mild cognitive impairment. Collectively, the data support a gut–immune system-brain axis in which host genotype shapes microbiota, and microbial metabolites or antigens contribute to neurodegeneration. Future work must define responder phenotypes, optimise next-generation probiotics and integrate multi-omics profiling with biomarker-driven clinical trials to translate microbiota modulation into disease-modifying therapy for AD.

Gut microbiota and obesity

Ivana Božić Antić, Danijela Vojnović Milutinović — Fri, 14 Nov 2025 00:00:00 +0100

Obesity represents a multifactorial, systemic disorder strongly associated with adverse health outcomes, including cardiometabolic syndrome. Beyond caloric imbalance between caloric intake and expenditure, recent evidence highlights the essential role of gut microbiota in the development and progression of obesity and related metabolic dysfunctions. The gut microbiota, composed of diverse bacterial species, archaea, fungi, and viruses, influences host metabolism through the production of low-molecular-weight metabolites and gastrointestinal hormones, significantly modulating energy homeostasis, appetite regulation, and insulin sensitivity. Specific bacterial taxa are implicated in either promoting metabolic health or contributing to obesity through mechanisms involving chronic systemic low-grade inflammation, increased intestinal permeability, and altered energy harvest. Dysbiosis—marked by reduced microbial diversity and compositional imbalance—is consistently linked to enhanced adiposity and systemic inflammation. Dietary patterns are key modulators of gut microbial composition and function. This review underscores the complex interplay between dietary patterns, gut microbiota-derived metabolites and host endocrine responses, that contribute to dysregulation of gut–brain axis communication observed in obesity.

Cutaneous microbiota: role in skin diseases

Dušan Škiljević — Sat, 08 Nov 2025 00:00:00 +0100

Koža je najveći organ čoveka i predstavlja višestruku barijeru prema agensima iz spoljašnje sredine, ali ujedno i kompleksan ekosistem koji naseljava raznovrsna mikrobiota, koja igra ključnu ulogu u održavanju homeostaze kože i zaštiti domaćina od patogena. Mikrobiota kože je druga najveća po obimu kod čoveka, nakon mikrobiote creva, i obuhvata oko 40 triliona mikroorganizama, sa sledećim dominantnim filumima:

- Bakterije: Actinobacteria, Firmicutes, Proteobacteria i Bacteroidetes

- Gljivice: dominira rod Malassezia

- Virusi: uglavnom bakteriofagi, ali i humani virusi, kao što je humani papiloma virus

- Arheje: dominira klasa Nitrososphaeria.

Kutana mikrobiota je manje raznovrsna od crevne, ali izuzetno složena. Na njen sastav utiču brojni endogeni (uzrast, pol, varijacije u genomu i imunskom odgovoru) i egzogeni faktori (geografski i klimatski faktori, razlike u životnim navikama, uzimanje lekova). Zahvaljujući svojoj topografskoj organizaciji sa zonama koje imaju različite mikroklimatske uslove, na koži postoje različita područja (“niše”) koje imaju specifičnu strukturu mikrobiote. Među najvažnijim ekološkim faktorima koji utiču na sastav mikrobiote jedne zone kože spadaju: količina sebuma u toj zoni, fluktuacije temperature, nivo vlažnosti, prisustvo pregiba i prevoja kože, sastav antimikrobnih lipida i peptida.

Osim dokazane uloge u očuvanju kutane barijere, mikrobiota kože svojim uticajem na imunski sistem, metaboličkom aktivnošću i uzajamnom regulacijom sa drugim mikrobiomima, dodatno doprinosi održavanju zdravlja kože i celog organizma.

Poremećaj homostaze mikrobiote sa poremećajem diverziteta u ekosistemu kože (disbioza) se danas smatra važnim faktorom u patogenezi različitih oboljenja kože, kao što su atopijski i seboroični dermatitis, psorijaza, supurativni hidradenitis, akne, rozacea. Takođe, razumevanje uticaja mikrobiote na razvoj različitih kutanih oboljenja dovelo je i do pojave prvih terapijskih modaliteta koji su zasnovani na modulaciji profila mikroorganizama, kao što su transplantacija mikrobiote i terapija bakteriofagima.

The role of the gut microbiota in inflammatory bowel diseases

Jelena Martinov Nestorov, Aleksandra Sokić Milutinović — Tue, 18 Nov 2025 00:00:00 +0100

The gut microbiota plays a pivotal role in maintaining gastrointestinal homeostasis and regulating immune responses. Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are associated with significant alterations in the composition and function of the intestinal microbiota—referred to as dysbiosis. Dysbiosis may contribute to impaired mucosal barrier function, heightened inflammation, and abnormal immune responses. The mechanisms by which microbiota influences the course of IBD include altered production of short-chain fatty acids, reduced microbial diversity, and an imbalance between protective and pathogenic bacteria. Interactions between the microbiota and immune cells, and their roles in initiating and sustaining inflammation, are subjects of ongoing research. Therapeutic strategies aiming to modulate gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), show promise in alleviating symptoms and prolonging remission in IBD patients. A deeper understanding of the complex role of the microbiota paves the way for personalized medicine and novel therapeutic approaches in the management of inflammatory bowel diseases.

Gut microbiome and bacterial resistance to antibiotics: reservoir or defence?

Dragana Vuković — Sun, 09 Nov 2025 00:00:00 +0100

Antibiotics have fundamentally transformed modern medicine, but their widespread use and misuse have led to the escalating crisis of antimicrobial resistance (AMR) in bacteria. Today, bacterial AMR represents a critical global health threat with severe medical and economic consequences. It is estimated that nearly five million deaths worldwide are linked to bacterial AMR each year.

While vital for maintaining host health, the human gut microbiome also harbors a collection of antibiotic resistance genes (ARGs), collectively known as the gut resistome. Numerous studies have shown that the gut resistome serves as a reservoir for ARGs, which can be mobilized and transferred to both commensal and pathogenic bacteria through horizontal gene transfer. Antibiotic exposure is major factor that disrupts the diversity and function of the gut microbiome, leading to the proliferation of resistant bacteria and the accumulation of ARGs. These changes, in turn, facilitate the further spread of resistance among bacterial populations.

Conversely, one of the gut microbiome’s key functions is to prevent the colonization and proliferation of both external pathogens and resident pathobionts, including bacteria resistant to antibiotics. This protection is mediated through mechanisms such as resource competition, metabolic interactions, and modulation of the host immune response. By limiting the colonization and expansion of resistant bacteria, the gut microbiome helps reduce the incidence of related infections and may contribute to lowering the overall burden of AMR.

This review explores the dual role of gut microbiome in the dynamics of bacterial AMR, both as a reservoir for the emergence of AMR and a critical line of defense against its spread. The review also highlights key research gaps that need to be addressed to promote development of targeted microbiome-based strategies for combating bacterial AMR effectively.