Pope Francis told Europe's leaders on Friday the continent faced a 'vacuum of values' as they marked the EU's 60th birthday, condemning anti-immigrant populism and extremism that he said posed a mortal threat to the bloc.

Prime ministers and presidents from 27 EU member states have descended on Italy to mark the 1957 founding Treaty of Rome, receiving a papal blessing on the eve of the anniversary.

However, celebrations have been tempered by a string of crises, including prolonged economic turmoil, an influx of migrants and Britain's decision to leave the bloc, that have raised fears for the future of the union.

'When a body loses its sense of direction and is no longer able to look ahead, it experiences a regression and, in the long run, risks dying,' Francis told the leaders gathered in an ornate, frescoed chamber in the heart of the Vatican.

Just six nations signed the original treaty in 1957 and on many levels the EU can be viewed as a success, swelling to embrace 28 countries gathered in the world's largest trading bloc and blessed with rising life expectancy and solid prosperity.

But with anti-European parties gaining support, the pope warned of a growing split between EU citizens and their institutions and said greater solidarity was the 'most effective antidote to modern forms of populism'.

The Argentinian-born pontiff told the leaders they needed to promote Europe's 'patrimony of ideals and spiritual values' with greater passion and vigour.

'For it is the best antidote against the vacuum of values of our time, which provides a fertile terrain for every form of extremism,' he said, mentioning the attack in London this week by a British-born convert to Islam, who killed four people.

The Pope has repeatedly criticised Europe over the past five years for its perceived lack of vision, drawing the ire of German Chancellor Angela Merkel in 2014 when he described the EU as an elderly woman who was 'no longer fertile and vibrant'.

He adopted a less hostile tone on Friday, but urged the continent not to close in on itself and resurrect walls – a message aimed as much at US President Donald Trump as at EU leaders struggling to deal with mass immigration.

Some 1.6 million refugees and migrants reached the European Union between 2014 and 2016 and how to handle them has been a major point of contention between member states.

'It is not enough to handle the grave crisis of immigration of recent years as if it were a mere numerical or economic problem, or a question of security,' the Pope said.

He decried a worrying 'lapse of memory' where people see today's immigrants fleeing war and hunger as a threat to a comfortable lifestyle, forgetting that modern Europe sprang from the ashes of World War Two and mass migration.

Thousands of demonstrators are expected to take to the streets of Rome on Saturday in at least six different rallies called by numerous groups across the political spectrum to protest against various aspects of EU rule.

Some 5,000 police have been called up to patrol the streets and the interior ministry has warned it will crack down swiftly on any violence.

Anti-migrant posters have been plastered on boards across the city, calling people to join one of the many marches to put pressure on the EU to turn back the newcomers.