Metaphorically speaking (and taken at the higher level comparison), the Europeans, were exploring for alternative ways to the Asian trade routes without the middle man. In effect, they were just doing a form of "hacking" -- finding an easier way to their goal and upsetting the status quo.

In some ways, that's similar to how most of us try to do in our own ventures what drives progress. It's fairly easy to ignore the consequences involved in disrupting a market, but holding back progress generally has a negative outcome for humanity as a whole.* It may have caused the Middle East to become more isolated, but at the same time, humanity needs to find a way to avoid repeating itself (as we still see such things even today in any rural part of the world). Open communication and integration generally leads to a more free exchange of ideas and calms fears between different cultural groups and nationalities.

*I'm ignoring the ethical consequences here that came with finding North/South America and focusing on the trade routes to avoid going too far off the subject.

There is no question that opening up direct trade routes has been beneficial overall for the world. But it wasn't for the Middle East, and the reasons for the decline, being distant, were not immediately apparent to anyone.

More generally everyone who has learned even a little economics knows that when you open up trade, you improve production. That's the whole point of comparative advantage. However lurking in the math is that if 2 parties are engaged in trade, and the third is not, adding the third makes the total better off, but is not necessarily better for all parties.

Agreed. I don't think anyone, even if it happened today would have saw the Middle East's gradual isolation over several hundred years as the likely outcome of Europeans "hacking" the silk road trade routes (though if a similar case happened today, it would probably be far less gradual). There were other factors as well, such as consecutive bad leadership in the Ottoman Empire following Suleiman the Magnificent (which is often cited as a big reason for the decline of the Western Roman Empire), but the consequences of the trade route disruption has too many ripple effects over time it's hard to say what or what was not in some way attributed to it.

Comparing the Ottomans and the Western Romans once again, both lost out on most of their profitable trade (as most of the trade was in the Eastern half of the Roman Empire and was no longer filling the Western tax coffers when the Empire split into two). Although I wouldn't take my conclusion as fault proof, but it would appear that countries can survive a string of bad leaders, but if trade that's taken for granted dries up and never returns, then the country is in bad shape if it cannot adapt.