Trace elements in human physiology and pathology. Copper Original paper

What was reviewed?

This review explains trace elements in human physiology and pathology, copper, and shows how copper acts as a vital cofactor yet turns toxic when unbound. The authors describe copper’s redox roles in respiration, antioxidant defense, iron handling, and connective tissue support, and then detail the tight homeostasis that keeps free copper near zero. They outline intestinal uptake, blood transport on albumin and transcuprein, delivery by chaperones to cuproenzymes, and ATP7A/ATP7B-driven export and biliary excretion. They also link copper excess to reactive oxygen species and protein damage, and copper lack to failed enzyme function and anemia. The narrative sets a clinical frame for how inflammation, diet, and genetics shift copper pools that microbes experience at mucosal sites.

Who was reviewed?

The review compiles data from human physiology, animal studies, and cell models to map copper movement from gut to liver and tissues. It discusses enterocyte uptake through CTR1, buffering by glutathione and metallothionein, and organ delivery via chaperones such as ATOX1, CCS, and COX17. It covers Menkes disease and Wilson disease as examples of failed ATP7A/ATP7B trafficking, and it explains how ceruloplasmin carries most serum copper and supports iron export. The authors also describe how inflammatory cytokines raise ceruloplasmin levels, how zinc therapy lowers intestinal copper uptake, and how biliary excretion dominates copper loss. This broad scope gives clinicians concrete host markers that shape the metal landscape for the microbiome and invading pathogens.

Most important findings

The review shows that copper must remain protein-bound to avoid tissue injury while still feeding key enzymes. It highlights cytochrome c oxidase and Cu/Zn-SOD as sentinel cuproenzymes that fail early in copper lack, and it places metallothionein as a major buffer that sequesters excess copper and limits radical damage. It explains how CTR1 pulls copper into enterocytes, how ATOX1 hands copper to ATP7A/ATP7B in the trans-Golgi for enzyme loading or efflux, and how ceruloplasmin carries the bulk of circulating copper. Inflammation raises serum ceruloplasmin, shifting exchangeable copper and likely the metal tone at the mucosa.

The review also details how high zinc or tetrathiomolybdate reduces copper absorption, and how bile flow controls whole-body copper balance. For a microbiome signatures database, these points translate into actionable host and microbial markers: host ATP7A/ATP7B variants, high ceruloplasmin states, and zinc therapy predict lower luminal copper; high biliary copper flow or impaired Wilson protein can raise gut copper; microbial tolerance modules such as CueO/CopA/Cus in Enterobacterales or cop operons in enterococci signal capacity to persist when copper rises during inflammation.

Key implications

Clinicians can read copper balance as both a systemic measure and a local ecological force. Inflammation that elevates ceruloplasmin may increase copper delivery to sites where microbes compete, favoring copper-tolerant taxa and restraining sensitive commensals. Zinc therapy for Wilson disease or deliberate zinc use can depress intestinal copper, which may ease copper stress on the gut microbiome but also reduce host cuproenzyme activity if carried too far. Reporting host markers such as ceruloplasmin, ATP7A/ATP7B status, and bile flow alongside microbial copper-handling genes can improve risk calls for dysbiosis or infection in the inflamed gut, biliary disease, or device-adjacent mucosa. These data support careful copper modulation in nutrition and device use and argue for restraint with metal exposures that could select for copper-tolerant pathobionts.